Department
of
Clinical Investigation
Annual Research Progress
Report
Fiscal Year 2006
Madigan Army Medical Center
Tacoma, Washington
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4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER
Madigan Army Medical Center
Annual Research Progress Report
Fiscal Year 2006
5b. GRANT NUMBER
5c. PROGRAM ELEMENT NUMBER
6. AUTHOR(S)
Barbara Jones, Troy Patience, Lucy Atoigue, Athena Rayner,
Mary Porreca, Jill Lund, Lissette Arroyo-Ortiz, MAJ Nancy
Merrill, Dr. Lonnie Lai, CPT Michael Hartenstine, COL Paul
Amoroso
5d. PROJECT NUMBER
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7. PERFORMING ORGANIZATION NAME(S) AND ADDRESS(ES)
Dept, of Clin. Investigation
Madigan Army Medical Center
Bldg. 9040, Fitzsimmons Dr.
Attn: MCHJ-CI
Tacoma, WA 98431-1100
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Clinical Investigation
Regulatory Office
Attn: MCCS-GCI, Bldg 2268
1608 Stanley Rd, Suite 2
Fort Sam Houston, TX 78234
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13. SUPPLEMENTARY NOTES
THE FINDINGS IN THIS REPORT ARE NOT TO BE CONSTRUED AS AN OFFICIAL DEPARTMENT OF THE ARMY
POSITION UNLESS SO DESIGNATED BY OTHER AUTHORIZED DOCUMENTS.
14. ABSTRACT
This report covers all research protocols that were administratively or technically supported
by the Department of Clinical Investigation, Madigan Army Medical Center, Tacoma, WA during
FY 2006. Included in the individual data summary sheets are title, investigators, objective,
technical approach, and progress for FY 2006. Also included in the report are personnel
rosters for the program, funding information, presentations, and publications emanating from
Madigan Army Medical Center during FY 2006. 127 new protocols were approved and 103 were
completed in FY 2006. 222 staff members, 79 residents/fellows and 18 non-Medical Corps
trainees held approved research protocols in FY 2006. 93 manuscripts were published as well
as 53 abstracts and 163 presentations.
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552
19a. NAME OF RESPONSIBLE PERSON
Paul J. Amoroso, COL, MC
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(253) 968-1160, DSN 782-
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REPORTS CONTROL SYMBOL RCS MED-300(R1)
ANNUAL PROGRESS REPORT
30 SEPTEMBER 2006
DEPARTMENT OF CLINICAL INVESTIGATION
MADIGAN ARMY MEDICAL CENTER
TACOMA, WASHINGTON 98431
THE FINDINGS IN THIS REPORT ARE NOT TO BE CONSTRUED AS AN OFFICIAL
DEPARTMENT OF THE ARMY POSITION UNLESS SO DESIGNATED BY OTHER
AUTHORIZED DOCUMENTS.
DESTROY THIS REPORT WHEN NO LONGER NEEDED.
DO NOT RETURN IT TO THE ORIGINATOR.
APPROVED FOR PUBLIC RELEASE
DISTRIBUTION UNLIMITED
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Table of Contents
Introduction & Acknowledgments . 8
Foreword . 9
Objective, Technical Approach, Staffing . 13
Research Funding . 14
Progress & Program Support . 15
Committee Members . 16
Awards
Graduation Awards . 18
Madigan Research Day Awards . 19
Presentations . 21
Publications . 32
Exempt Protocols . 38
Detailed Summary Sheets - Table of Contents . 39
Department of Anesthesia & Operative Services . 64
Department of Clinical Investigation . 67
Hospital Dental Clinic . 80
Department of Emergency Medicine . 82
Department of Family Medicine . 89
Graduate Medical Education . 106
Health Outcomes Management Division . 108
Cardiology Service, Department of Medicine . Ill
Hematology/Oncology Service, Department of Medicine . 114
Internal Medicine Service, Department of Medicine . 200
Nephrology Service, Department of Medicine . 216
Neurology Service, Department of Medicine . 218
Pulmonary Disease & Critical Care Service, Dept, of Medicine .. 226
Nutrition Care Division . 232
Department of Nursing . 234
Anesthesia Students, Department of Nursing . 250
Department of Obstetrics/Gynecology . 252
Department of Pathology . 280
Department of Pediatrics . 285
Department of Pharmacy . 343
Department of Psychiatry . 352
Department of Psychology . 356
Department of Radiology . 362
Special Forces . 370
General Surgery Service, Department of Surgery . 373
Ophthalmology Service, Department of Surgery . 429
Orthopedics Service, Department of Surgery . 436
Otolaryngology Service, Department of Surgery . 461
Urology Service, Department of Surgery . 478
Vascular Surgery Service, Department of Surgery . 527
Weed Army Community Hospital . 546
Index with Protocol Numbers . 549
Annual Report Distribution List . 552
7
FISCAL YEAR 2006
DEPARTMENT OF CLINICAL INVESTIGATION
MADIGAN ARMY MEDICAL CENTER
TACOMA, WASHINGTON 98431
Introduction
In conducting the research described in this report, the investigators adhered to the
“Guide for the Care and Use of Laboratory Animals” as prepared by the Committee on the
Care and Use of Laboratory Animals of the Institute of Laboratory Animal Resources,
National Institutes of Health, and Title 9, Subchapter A, Parts I, II, and III of the Code of
Federal Regulations. The investigators adhered to Title 21, Part 50 of the Code of Federal
Regulations and the recommendations from the Declaration of Helsinki in the
performance of investigations involving human subjects.
Acknowledgments
The DCI staff would like to acknowledge the significant and varied contributions of
many individuals and organizations, all of whom were instrumental in making Madigan
Army Medical Center (MAMC) research a resounding success in 2006. We appreciate the
support and participation of the Western Regional Medical Center (WRMC) Command
Leadership for fostering an environment where "Care with Compassion" is the motto and
meticulous scientific process is the standard. We would like to thank our many corporate
and industry research sponsors and partners, especially those foundations that foster
military, medical research and support the Madigan community. We also would like to
acknowledge the dedicated members of the Madigan Institutional Animal Care and Use
Committee (IACUC), the Clinical Investigation Committee (CIC), and the Human Use
Committee (HUC) whose tireless efforts ensured quality science and ethical conduct of our
research. And, last but certainly not least, we would like to thank the hundreds of
MAMC’s military health care beneficiaries who volunteered to participate in so many
demanding research studies, often when the only conceivable benefits were to individuals
other than themselves.
8
Foreword
Clinical Studies Service (CSS)
The Clinical Studies Service has as its mission to increase the quantity and the
quality of clinical trials that are open and available to military beneficiaries. This is
accomplished by working with investigators in the clinics to determine their research
interests, commonly seen disease states, and logistical hurdles to implementing trials.
The goal is that each clinic have the support staff necessary to offer patients clinical trial
options for most commonly seen diseases.
Successful collaborations over the past year include progress toward participation
as the only IRB outside of the National Capitol Area to join the United States Military
Cancer Institute IRB. Successes in terms of hiring research personnel include
participation with USUHS to provide a 3-year grant to hire a research nurse to the
Hematology/Oncology Clinic and offering a contract to a physician-researcher to perform
clinical trials within primary care clinics, primarily Internal medicine and Family
Practice. Other successes include recruiting clinical trials to multiple specialty services,
including Cardiology, Oncology, Orthopedic Surgery, and Cardiothoracic Surgery.
The goals for the next year are to recruit clinical trials to MAMC that will allow
hiring of research staff in the Family Medicine, Neurology, and Emergency Medicine
services, improve the collaboration with the USMCI, and represent MAMC interests with
CIRO in simplifying and standardizing research protocols and IRB practices, with a goal
of increasing collaboration between military medical centers.
Laboratory Animal Resources Service (LARS)
LARS remains heavily involved in the trauma training course offered to combat and
combat support units of Ft. Lewis and other units under the Western Regional Medical
Command. This course has trained over 220 medics, physician assistants, nurses, and
doctors in combat trauma management; 64 Emergency Department residents in
emergency procedures; 14 urology residents and 24 surgery residents in advanced
laparoscopic techniques; and 88 providers in pediatric intubation. LARS has supported
the training of more than 72 Special Forces medics. There is increased collaboration
between LARS, the Anderson Simulation Center, and the Medical Simulation Training
Center to stay current with simulator technology which reduces the number of animals
required for effective training. The newt limb regeneration study is ongoing. LARS
supports research studies involving cancer metastasis, hypoperfusion/reperfusion injuries,
and acute inflammatory reactions. There are new protocols being planned to study
effectiveness of a new hemorrhage control material.
Research Administration Service (RAS)
FY06 was a typically busy year for RAS with a total of 127 new protocols and 460
active protocols. New initial and continuing review protocols continued to show 100%
9
HIPAA compliance. New protocols reviewed at convened IRB meetings averaged less than
those in FY05 overall, but the numbers of ERC protocols increased slightly. However,
formal research conducted in MAMC and the Western Regional Command Medical
continues to be a solid and viable program. No RAS personnel staffing changes have
occurred.
The internal audit program continues to be refined, with 21 protocols having been
audited. Most audits have shown satisfactory results; however, findings in one instance
raised concern about the conduct of retrospective review protocols and the use of subject’s
protected health information. The number of audits planned during FY07 will be double
those conducted in FY06 and will include a few minimal risk retrospective review
protocols to ascertain whether the use of codes and the de-linking procedures described in
the protocol are being adequately carried out.
The RAS/Protocol Management Quality Improvement Team has continued to refine
and implement improvements to local IRB administrative policies and procedures:
1. Updated entire SOP book in preparation for FDA inspection, which RAS is still
awaiting.
2. Begun consolidating human use protocol template into one universal format for
local and multicenter studies.
3. Turned the Expedited Review Committee (ERC) into a weekly (as needed)
meeting for reviewing ERC eligible protocols.
Participated in coordinating 2 semi-annual Applied Research Training (ART) Courses
(formerly called Introduction to Clinical Research Course), which are held in collaboration
with the MAMC Faculty Development Fellows. Attendance averages about 50 students.
Additionally, investigators are still obtaining the required Human Subjects Protections
training through DCI’s subscription with the University of Miami’s Collaborative IRB
Training Initiative (CITI).
In FY07, RAS plans to:
(1) implement a universal human use protocol template;
(2) continually expand the DCI website to offer more information and reporting
options for investigators;
(3) continue to develop and refine the constructive internal audit program;
(4) participate in planning the semi-annual ART Course and annual Madigan
Research Day;
(5) work more closely with the Foundations (Geneva, Jackson, and True) to improve
communication for the research program;
(6) host and conduct the annual DCI HELPER Course for research coordinators
working within MAMC.
Research Operations Service (ROS)
DCI’s Research Operations Service at Madigan Army Medical Center experienced
continuing growth in FY 2006. Acquisition of a SELDI-TOF mass spectrophotometer
ushered in the official start of high throughput proteomics work at Madigan. The SELDI
10
technology offers enormous potential for protein biomarker discovery in the analysis of
clinical samples and application to ongoing research projects. ROS made significant
progress introducing the SELDI-based high throughput proteomic capabilities to MAMC.
In our initial longitudinal studies of the human Pregnancy Proteome, study staff enrolled
and collected samples at various points of gestation from over 110 patients. ROS also
welcomed three new medical technologists to the lab who will be essential in supporting
recent increases in GME research activity at MAMC. The laboratory maintained active
basic research protocols with 4 of 6 medical departments at MAMC including the
departments of Surgery (General Surgery, Urology, and Orthopedics), Pediatrics,
Pathology, and OB/GYN (Maternal Fetal Medicine Fellowship). Residents won 2 separate
awards at the 9th Annual Madigan Research Day for research conducted within the lab. In
further support of our GME mission, ROS hosted the 2006 DCI Molecular Biology Short
Course. The 5-day lab and lecture course provides novice clinical researchers with
perspective on modern molecular and cellular biology techniques and the relationship
between basic and clinical research. The ROS laboratory made marked progress on
several basic science research protocols including but not limited to the following: a)
methods for creating transgenic plants to produce proteins of clinical, environmental and
military-unique utility; b) development of cell-based assays against neurotoxins and
characterization of G protein coupled receptors using neurons derived from mouse
embryonic stem cell culture; c) characterization of the CXCR4/SDF-lalpha chemokine axis
as a potential means of directing therapeutic cells to damaged tissue; d) characterization
of the molecular mechanisms of limb regeneration in newts. ROS maintained an active
internship program with Bates Technical College wherein interns gain valuable real world
experience while increasing laboratory productivity. In FY07, ROS looks forward to
promoting sustainable and synergistic research efforts among laboratory staff and medical
center residents in support of our graduate medical education mission.
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UNIT SUMMARY - FISCAL YEAR 2006
A. Objective:
Provide and create an environment to support clinical and basic medical research within Madigan
Army Medical Center. Clinical Investigation exists to further the highest degree of medical
readiness. DCI supports the Graduate Medical Education mission through leadership in curriculum
development, medical education research, and military unique clinical investigations, as well as
training opportunities available through institutional programs (ATLS, PALS, etc.).
B. Technical Approach:
All research, investigational and training activities within the Department of Clinical Investigation
are conducted under the guidance of the Office of Human Research Protections (OHRP), Food &
Drug Administration (FDA), AR 40-7, AR 40-38, AR 70-25, and AR 40-33. Careful monitoring of all
approved protocols is conducted in order to assure strict compliance with the applicable regulations.
C. Staffing:
Name
Rank
MOS
Title
Amoroso, Paul
COL
61N
Chief, DCI
*Myers, Jerome
COL
61U
Chief, DCI
°McCune, David
LTC
61B
Clinical Trials Director
Arroyo -Ortiz, Lissette
GSll
0671
Health System Specialist
Patience, Troy
GSll
1530
Statistician (Medicine)
Atoigue, Lucy
GS06
0318
Secretary/Steno
Porreca, Mary
GS05
0303
Research Protocol Clerk
Merrill, Nancy
MAJ
64C
Chief, Lab Animal Res Svc
*Gibson, Steven
GSll
0301
Trauma Training Specialist
Karen Van Loon
MSG
91T
Animal Technologist & NCOIC
*Phyall, Shayla
SPC
91T
Animal Technologist
Phillips, Miemie
SPC
91T
Animal Technologist
Spahn-Bridges, Shelley
WG05
5048
Animal Caretaker
*Theis, Jennifer
GSll
0301
Trauma Training Specialist
*McNutt, Patrick
CPT
71B
Chief, Research Op Svc
“Celver, Jeremy
CPT
71A
Cell Biologist
Hartenstine, Michael
CPT
71B
Molecular Biologist
*Fannings, Anthony
SSG
91K
NCOIC
Wright, James
GSll
0644
Medical Technologist
Bullock, Jeff
GSll
0644
Medical Technologist
DeHart, Mary
GSll
0644
Medical Technologist
*Murcin, Lara
GSll
0644
Medical Technologist
*Cederholm, Heidi
GSll
0644
Medical Technologist
*Bergmann, Aspen
GSll
0644
Medical Technologist
*Ippolito, Danielle
GSll
0644
Medical Technologist
Lai, Lonnie
GS13
0601
Chief, Research Administration Svc
Jones, Barbara
GSll
0301
Research Protocol Manager/Auditor
Rayner, Athena
GS09
0303
Research Protocol Specialist
Lund, Jill
GS07
0303
Research Protocol Assistant
LEGEND l*denotes staffing status change!
*Myers - PCS’d in Jul 2006
*Phyall - PCS’d in Nov 2006
*McNutt - PCS’d in Sep 2006
*Murcin - Resigned in Oct 2005
*Bergmann - New Hire in Feb 2006
*Gibson — Resigned in Jan 2006
*Theis - New Hire/Promotion in Oct 2005/Jul 2006
*Fannings - PCS’d in Jun 2006
*Cederholm - New Hire in Feb 2006
*Ippolito - New Hire in May 2006
°McCune & Celver — Assigned part time
13
Summary:
Personnel:
Authorized Required
Assigned
Officers
4 4
4
Civilians
17 19
17
Enlisted
4 4
4
D. Funding:
P8 Funds
Civilian Payroll
$1,036,814
Operations
$149,550
CEEP
$286,941
TDY (CHE)
$11,290
TDY (for researchers to present)
$41,734
Reproduction Requests
$1,717
Contracts
$7,629
MEDCASE
$0
Military Payroll (est.)
P8 funds total
$558,232
MAMC Resource Management Division Oversight
Air Force (support for MFM) $54,000
Military units (support for Combat Trauma Training) $71,932
Internal oversight total
Grants Federal
Henry M. Jackson Foundation $203,135
The Geneva Foundation (Tri-Service Nursing) $335,362
T.R.U.E. Foundation $964
Federal grant total
Grants Nonfederal
Henry M. Jackson Foundation (CRADA) $146,111
The Geneva Foundation (CRADA) $334,876
Non-federal grant total
FY06 Research Resources Total
$2,093,907
$125,932
$539,461
$480,987
$3,240,287
14
E. Progress
During FY 2006, there were 464 active protocols that received administrative and/or
technical support during the year, of these, 317 are presently ongoing, 3 are in a
suspended status, 99 were completed, 40 were terminated, 4 are IACUC expired protocols.
The principal investigator distribution was as follows: 333 staff protocols, 85 resident
protocols, 18 fellow protocols, and 2 Special Forces animal protocols. There were 127 new
protocols, of which 10 were Exempt, 59 were ERC, 48 were IRB, and 10 were IACUC
protocols.
There were 93 publications in publicly available sources and 163 presentations at
regional or national meetings.
F. Program Support
Programs supported by DCI: 10 internships, 15 residencies, 5 fellowships, and 7 non-
MC programs; they are:
Internships : Emergency Medicine, Family Practice, General Surgery, Internal
Medicine, Neurology, Obstetrics and Gynecology, Orthopaedic Surgery, Pathology,
Pediatrics, and Transitional Year.
Residencies : Emergency Medicine, Family Practice, General Surgery, Internal
Medicine, Neurology, Obstetrics and Gynecology, Ophthalmology, Oral and Maxillofacial
Surgery, Orthopaedic Surgery, Otolaryngology, Pathology, Pediatrics, Preventive Medicine
(Public Health), Radiology (Diagnostic), and Urology.
Fellowships'. Developmental Pediatrics, Faculty Development (Family Practice),
Geriatric Medicine, Maternal-Fetal Medicine, and Urogynocology.
Non-MC programs'. Diabetic Foot Fellowship, Occupational Therapy, Pediatric
Psychology, Pharmacy Practice, Physician Assistance Program (Emergency Medicine &
Orthopaedics), and Podiatry.
Other training protocols supported by DCI:
DCI: 203023, 203077, 203092, 206109
Department of Surgery: 203016, 204058, 204101, 205017, 205079, 206030
Department of Emergency Medicine: 204028, 206078
Special Forces: 206018, 206106
15
G. Committee Members
Clinical Investigation Committee
COL Paul J. Amoroso, MC
Chairman
Chief or delegated representative of:
Department of Emergency Medicine
Department of Family Medicine
Department of Medicine
Department of Nursing
Department of OB/GYN
Department of Pathology
Department of Pediatrics
Department of Pharmacy
Department of Preventive Medicine
Department of Radiology
Department of Surgery
Physical Medicine & Rehabilitation Service
Department of Clinical Investigation (DCI)
Clinical Studies Service, DCI
Medical Statistician, DCI
Research Administration Service, DCI
Research Operations Service, DCI
General Surgery Research Resident, DCI
16
Human Use Committee
COL Paul J. Amoroso, MC
Chairman
Chief or delegated representative of:
Department of Nursing
Department of Pathology
Department of Pediatrics
Department of Pharmacy
Department of Radiology
Department of Ministry and Pastoral Care
Research Administration Service, DCI
Social Work Service
Center Judge Advocate
Non-institutional Member
Institutional Animal Care & Use Committee
MAJ Andrew C. Peterson, MC
Chairman
Chief or delegated representative of:
Department of Clinical Investigation (DCI)
Department of Pathology
Department of Medicine
Department of Surgery
Non-affiliated Member and Alternate Non-affiliated Member
Attending Veterinarian, DCI
Animal Care Worker, DCI
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H. Awards
Each of the following awards was judged based on a submitted manuscript.
Major General Byron L. Steger Research Award
This award is given to a resident, submissions are judged on their scientific merit,
relevance, objectivity of evaluation, interpretation of results, and the potential importance
of the subject of the research
Recipient of this award for 2006: CPT James Wang, MC
Manuscript: Efficacy of Iron in Patients with Restless Legs Syndrome and a Low-Normal
Ferritin: A Randomized, Double-Blind, Placebo Controlled Study
COL Patrick S. Madigan Foundation Research Award
This award is given to a fellow, submissions are judged on their scientific merit, relevance,
objectivity of evaluation, interpretation of results, and the potential importance of the
subject of the research.
Recipient of this award for 2006: MAJ Jennifer L. Gotkin, MC
Manuscript: Progesterone Reduces Lipopoly saccharide Induced Interleukin- 6 Secretion in
Fetoplacental Arteries, Fractionated Cord Blood, and Maternal Mononuclear Cells
Major General Kenyon Joyce Award
This award is given to staff, submissions are judged on their scientific merit, relevance,
objectivity of evaluation, interpretation of results, and the potential importance of the
subject of the research.
Recipient of this award for 2006: LTC Bobby C. Howard, MC, USAF
Manuscript: A Comparison of Oxytocin Requirements in Patients Randomized to Elective
Induction of Labor versus Expectant Management
18
Madigan Research Day Awards
These awards are given after Madigan’s Annual Madigan Research Day to recognize the
best presentation in the each of the following six sessions: Military Unique Clinical
Investigation, Medical Education Research, Experimental Design, Managed Care/Health
Outcomes, Case Report, and Poster. This year’s winners are:
Military Unique Clinical Investigation - CPT Julie Ake, MC for presentation entitled
“Risk Behavior, Knowledge and Attitudes of ROTC Cadets Regarding HIV/AIDS”
Medical Education Research (tie) - MAJ Aaron Saguil, MC for presentation entitled
“The Role of Evidence and Other Determinants in Family Medicine Resident Physician
Discussions of Spirituality with Patients”
Medical Education Research (tie) - MAJ Jean Jones, AN for presentation entitled
“Junior Army Nurse Corps (ANC) Officers’ Experiences & Expectations of Head Nurse
(HN) Leadership”
Case Report - CPT Kerry O’Brien, MC for presentation entitled “Managing Patients with
Rare Antibodies and Multiple Medical Issues is a Difficult Problem Requiring a Team
Approach”
Experimental Design - CPT Garth Herbert, MC for presentation entitled
“Intraperitoneal LPS Delivery in Mice Causes Multi-organ, Coordinated Modulation of
SDF-la Production over a 72-Hour Period”
Managed Care/Outcome Studies - CPT Jeffrey Tebbs, MS for presentation entitled
“Decreasing Behavioral Restraint Use: A Workload Management Approach”
Poster - 1LT Robin Smith, AN for presentation entitled “An Evidence-Based Clinical
Intervention Strategy to Reduce Falls: The Next Generation”
Special awards presented during Madigan Research Day:
BG GEORGE J. BROWN MENTOR’S CUBE
The BG George J. Brown Mentor's Cube honors the vital role of the mentor in the
process of medical education and research. Madigan Research Day celebrates the breadth
and depth of scholarly activity performed at MAMC. The BG George J. Brown Mentor's
Cube honors this vital core attribute of excellence in medical scholarship.
Presented to: LTC Peter Napolitano, MC
Department: Obstetrics/Gynecology
19
NANCY J. WHITTEN OUTSTANDING IRB MEMBER AWARD
An IRB is a committee designated by an institution to review, to approve the initiation
of, and to conduct periodic review of biomedical research involving human subjects. The
primary purpose of such review is to assure the protection of the rights and welfare of
human subjects. An outstanding IRB member goes the extra mile. This award was
created to honor those that contribute above and beyond the call of duty.
Presented to: COL Jerome Myers, MC
Department: Clinical Investigation
BG MACK C. HILL FACILITATOR’S AWARD
This award was created to recognize a Madigan member who has helped to facilitate
the center's research mission in ways that are not always apparent to the general
population. This individual represents the epitome of selfless service through their
continual and frequent transparent support of others success .... they exhibit a generous
customer service attitude.
Presented to: CPT Matthew Miller, JA
Department: Center Judge Advocate
BG MICHAEL DUNN ‘PRESS-ON’ AWARD
The award is an obelisk which signifies the interconnecting spheres of the physical,
mental and spiritual in the human experience. The BG Michael A. Dunn Award recognizes
that the attributes of persistence and determination are at least as, and perhaps, more
important than talent, genius or education in reaching meaningful goals. This award,
established in 2005, is presented annually to a member of the staff whose determination
has led to significant contributions in Research, Education, Patient Care and/or
Administrative Procedures over the past twelve months.
Presented to: CPT Jessica Arens, MS
Department: Psychiatry
20
I. Presentations
Department of Clinical Investigation
Merrill NL. US Army Veterinary Corps. Presented at WSU Swine Center, Pullman, WA, March
2006.
Department of Emergency Medicine
Blankenship RB. Web education: an introduction/overview. Presented at American College of
Emergency Physicians Advanced Teaching Fellowship, Albuquerque, NM, September 2006.
Blankenship RB. How to construct an online lecture. Presented at American College of Emergency
Physicians Advanced Teaching Fellowship, Albuquerque, NM, September 2006.
Blankenship RB. Deploying your Web training. Presented at American College of Emergency
Physicians Advanced Teaching Fellowship, Albuquerque, NM, September 2006.
Blankenship RB. Building Interactive Online Content. Presented at American College of
Emergency Physicians Advanced Teaching Fellowship, Albuquerque, NM, September 2006.
Blankenship RB. The Internet as an Educational Tool. Presented at Joint Services Symposium
2006, San Antonio, TX, March 2006.
Blankenship RB. Thrombosis of a Non-ruptured Abdominal Aortic Aneurysm in a 48 year-old
Female. Presented at Joint Services Symposium 2006, San Antoino, TX, March 2006.
Department of Family Medicine
Angwafo NN. Management of Cerebrospinal Fluid Rhinorrhea in Pregnancy. Presented at 9th
Annual Madigan Research Day, Tacoma, WA, April 2006.
Junnila JF. Do Race or Rank Predict Receipt of Pap Test in a Military Healthcare System?
Presented at USAFP Annual Scientific Meeting, Chicago, IF, March 2006.
Pflipsen MC. Vitamin B12 Deficiency in the Type 2 Diabetic Population. Presented at 9th Annual
Madigan Research Day, Tacoma, WA, April 2006.
Pflipsen MC, Oh RC, Saguil A. Vitamin B12 Deficiency in the Type 2 Diabetic Population: A
Preliminary Report. Presented at USAFP 2006 Annual Meeting and Exposition, Chicago, IF,
March 2006.
Runser FA. Esophagogastroduodenoscopy by a Family Physician: A Case Series Demonstrating
Healthcare Savings. Presented at 9th Annual Madigan Research Day, Tacoma, WA, April 2006.
Runser FA, Short MW. Upper Endoscopy by a Family Physician. Presented at AAFP National
Scientific Assembly, Washington, DC, September 2006.
Saguil AA. Residents and Patient Spirituality. Presented at American Academy of Family
Physicians Scientific Assembly, Washington, DC, September 2006.
Saguil AA. The Role of Evidence and Other Determinants in Family Medicine Resident Physician
Discussions of Spirituality with Patients. Presented at 9th Annual Madigan Research Day,
Tacoma, WA, April 2006.
21
Medical Education
Stillsmoking KL. Simulation Education: The Paradigm in Healthcare's Training Process.
Presented at ASSN of Perioperative Registered Nurses, Tacoma, WA, April 2006.
Internal Medicine Service, Department of Medicine
Abbott JT, Davis JL. Post operative complication after tricuspid / pulmonmic valve replacement in
a patient with metastatic carcinoid syndrome. Presented at Army American College of Physicians
Annual Meeting, San Antonio, TX, November 2005.
Ake JA. Risk Behavior, Knowledge and Attitudes of ROTC Cadets Regarding HIV/AIDS.
Presented at 9th Annual Madigan Research Day, Tacoma, WA, April 2006.
Ake JA, Coyle JR, Wojciehowski AO, Morris JT. Risk behavior, knowledge and attitudes of ROTC
cadets regarding HIV/AIDS. Presented at Army American College of Physicians Annual Meeting,
San Antonio, Tx, November 2005.
Ake JA, Erickson JC, Lowry KJ. Cerebral aneurysmal arteriopathy associated with adulthood
HIV infection. Presented at Army American College of Physicians Annual Meeting, San Antonio,
TX, November 2005.
Ake JA, Mysliwiec AG, Mysliwiec V. Intrathoracic granulocytic sarcoma presenting with pleural
effusion in a patient with CMML. Presented at Army American College of Physicians Annual
Meeting, San Antonio, TX, November 2005.
Bauler KC, Harner KC, Niven AS. A patient with progressive dyspnea and skin thickening: A
treatment dilemma. Presented at Army American College of Physicians Annual Meeting, San
Antonio, TX, November 2005.
Broy CC. Gitelman's Disease in a Patient with Nephrocalcinosis Secondary to
Hyperparathyroidism. Presented at 9th Annual Madigan Research Day, Tacoma, WA, April 2006.
Broy CC, Bennett SP. Partial Anomalous Pulmonary Venous Return. Presented at Army
American College of Physicians Annual Meeting, San Antonio, TX, November 2005.
Coyle JR, Harner KC. Dactylitis Secondary to Systemic Lupus Erythematosus. Presented at Army
American College of Physicians Annual Meeting, San Antonio, TX, November 2005.
DeHaan PJ, Mysliwiec V. An Unusual Case of an Exudative Lymphocyte- Predominant Pleural
Effusion. Presented at Army American College of Physicians Annual Meeting, San Antonio, TX,
November 2005.
DeHaan PJ, Rinard JP, Roth BJ. Dose adherence to the American Thoracic Society (ATS)
treatment guidelines for parapneumonic effusions affect outcome? Presented at Army American
College of Physicians Annual Meeting, San Antonio, TX, November 2005.
DeHaan PJ, Rinard JP, Roth BJ. Dose Adherence to the American Thoracic Society (ATS)
Treatment Guidelines for Parapneumonic Effusions Affect Outcome? Presented at American
College of Physicians Annual Meeting, Philadelphia, PA, April 2006.
Feaver AA, Derrick BC, Peterson CK. Results from the diabetes care center: A disease targeting
approach. Presented at Army American College of Physicians Annual Meeting, San Antonio, TX,
November 2005.
Feaver AA, Derrick BC, Peterson CK. Results from the diabetes care center: A disease targeting
approach. Presented at Army American College of Physicians Annual Meeting, Seattle, WA,
November 2005.
22
Feaver AA, Derrick BC, Peterson CK. Results from the Diabetes Care Center: A Disease Targeted
Approach. Presented at 9th Annual Madigan Research Day, Tacoma, WA, April 2006.
Fischer CJ, Gibson CA. Chronic urticaria: Resolution with total thyroidectomy. Presented at
Washington State American College of Physicians Annual Meeting, San Antonio, TX, November
2005.
Fischer CJ, Peterson CK, Watts JA. Subspecialty elective participation by internal medicine
housestaff and ABIM certification examination performance. Presented at SGIM Annual Meeting,
Los Angeles, CA, April 2006.
Kiley CA. Use of CT Scan Pulmonary Angiography (CTPA) in the Evaluation of Venous
Thromboembolism (VTE): An Examination of Hospital Referral Practices. Presented at 9th Annual
Madigan Research Day, Tacoma, WA, April 2006.
Kiley CA, Lowry KJ, Mysliwiec V. Use of CT Scan Pulmonary Angiography (CTPA) in the
Evaluation of Venous Thromboembolism (VTE): An Examination of Hospital Referral Practices.
Presented at American College of Physicians Annual Meeting, Philadelphia, PA, April 2006.
Kiley CA, Mysliwiec V, Lowry KJ. Use of CTPA in evaluation of venous thromboembolism - an
examination of hospital referral practices. Presented at Army American College of Physicians
Annual Meeting, San Antonio, TX, November 2005.
Kwon HP, Lowry KJ. Atypical sepsis in an intravenous drug user. Presented at Army American
College of Physicians Annual Meeting, San Antonio, TX, November 2005.
Kwon HP, Mysliwiec V. A Rare Case of Hemoptysis. Presented at Army American College of
Physicians Annual Meeting, San Antonio, TX, November 2005.
Owshalimpur D, Cushner HM, Lee JY, Starnes BW. Does high resistive index by Doppler
ultrasound predict small kidney. Presented at Army American College of Physicians Annual
Meeting, San Antonio, TX, November 2005.
Owshalimpur D, Kunz J, Kenwood B. Percutaneous treatment of a kinked LIMA. Presented at
Army American College of Physicians Annual Meeting, San Antonio, TX, November 2005.
Reilly SC, Lowry KJ. Failed Medical Management of a MRSA Sternoclavicular Septic Arthritis.
Presented at Army American College of Physicians Annual Meeting, San Antonio, TX, November
2005.
Sapp JE, Ake JA, Morris JT, Niven AS, Mysliwiec AG. Metastatic Melanoma in an HIV-Positive
53 year-old- male. Presented at Army American College of Physicians Annual Meeting, San
Antonio, TX, November 2005.
Wang JY. Efficacy of Iron in Patients with Restless Legs Syndrome and a Low-Normal Ferritin: A
Randomized, Double-Blind, Placebo Controlled Study. Presented at 9th Annual Madigan Research
Day, Tacoma, WA, April 2006.
Wang JY. Efficacy of iron in patients with restless leg syndrome and a low-normal ferritin: a
randomized, double-blind, placebo controlled study. Presented at SLEEP 2006 20th Anniversary
Meeting of the Associated Professional Sleep Society, Salt Lake City, UT, June 2006.
Wang JY, Fischer CJ, DeHaan PJ, Owshalimpur D, Mysliwiec AG. Efficacy of iron in patients
with restless legs syndrome and low-normal ferritin: a randomized, double-blind, placebo
controlled study. Presented at Army American College of Physicians Annual Meeting, San
Antonio, TX, November 2005.
Wang JY, McKinley BT, Lee JY. Atypical presentation of Sjogren's syndrome manifesting as acute
renal failure. Presented at Army American College of Physicians Annual Meeting, San Antonio,
TX, November 2005.
23
Wilton NK, Howden JK. Acute pancreatitis in a patient secondary to volvulus after simultaneous
pancreas and kidney transplant. Presented at Army American College of Physicians Annual
Meeting, San Antonio, TX, November 2005.
Witters RA, Lowry KJ. Linezolid and atypical mycobacteria. Presented at Army American College
of Physicians Annual Meeting, San Antonio, TX, November 2005.
Witters RA, Morris JT, Mahlen SD. A rare case of sepsis caused by Erysipelothrix Rhusiopathiae
bacteremia. Presented at Army American College of Physicians Annual Meeting, San Antonio, TX,
November 2005.
Wojciehowski AO, Rutberg S. Broken Hearts: A Case Series of Catecholamine Induced
Cardiomyopathy and Literature Review. Presented at Army American College of Physicians
Annual Meeting, San Antonio, TX, November 2005.
Neurology Service, Department of Medicine
Flynn FG. Update on Normal Pressure Hydrocephalus. Presented at 25th Annual AMEDD
Neurology Conference, San Antonio, TX, November 2005.
Hohler AD. Domestic Violence Education and Practice Improvement. Presented at American
Academy of Neurology, San Diego, CA, April 2006.
Hohler LD. Parkinsonism Related to Oral Ingestion of Manganese. Presented at American
Academy of Neurology, April 2006.
Lee JD. Neurological Perspectives in End of Life Care. Presented at Washington State Medical
Association Annual Meeting, Seattle, WA, September 2006.
Lee JD. Neurological Complications of Thermal Injury. Presented at American Academy of
Neurology, San Diego, CA, April 2006.
Scott BR. Horner Syndrome. Presented at Pacific Northwest Neuro-Ophthalmology Society
Meeting, Casey Eye Institute, Portland, OR, November 2005.
Theeler BJ. Prevalence and Impact of Migraine among U.S. Army Soldiers Deployed to a Combat
Theater. Presented at 9th Annual Madigan Research Day, Tacoma, WA, April 2006.
Theeler BJ, Mercer R, Erickson JC. Prevalence and Impact of Migraine Among U.S. Soldiers
Deployed to a Combat Theater. Presented at American Headache Society Annual Meeting, Los
Angeles, CA, June 2006.
Department of Nursing
Bryant JV. The Effects of St. John's Wort on Emergence Time from General Anesthesia in Male
Sprague-Dawley Rats (Rattus norvegicus) Undergoing Abdominal Surgery. Presented at 9th
Annual Madigan Research Day, Tacoma, WA, April 2006.
Carney LM. Call to duty: NP's on the Front Lines. Presented at AANP, June 2006.
Garner BK. ICU Restraint Protocol Initiative and Compliance in the Intensive Care Units.
Presented at 9th Annual Madigan Research Day, Tacoma, WA, April 2006.
Hopkins DL. Stress, Role Strain, Health & Attrition in Junior Enlisted Air Force Women with and
without Preschool Children. Presented at 38th Biennial Sigma Theta Tau International
Convention, Indianapolis, ID, November 2005.
Jones JM. Junior Army Nurse Corps (ANC) Officers' Experiences & Expectations of Head Nurse
(HN) Leadership. Presented at 9th Annual Madigan Research Day, Tacoma, WA, April 2006.
24
Jones JM, Loan LA, Cofield TS, Blackman LL. Junior ANC Officers' Experiences & Expectations
of Head Nurse Leadership. Presented at Phyllis J. Verhonick Nursing Research Conference, San
Antonio, TX, May 2006.
Kamara J. The Impact of Inpatient Physician Order Entry on Medication Administration Error
Rates in the Neonatal Intermediate and Intensive Care Units. Presented at 9th Annual Madigan
Research Day, Tacoma, WA, April 2006.
Raymond SM. From Numbers to Knowledge to Know-How: Using Pressure Ulcer Prevalence Data
to Improve Patient and Cost Outcomes. Presented at 9th Annual Madigan Research Day, Tacoma,
WA, April 2006.
Reyes SD, Looper R. Academic Readiness and Board of Nursing Examiners Brief. Presented at
AMEDD C & S Fort Sam Practical Nurse Educators Conference, San Antonio, TX, August 2006.
Ribbing SK. Effects of Chrysin on Emergence Time in Sprague-Dawley Rats after Laparotomy.
Presented at 9th Annual Madigan Research Day, Tacoma, WA, April 2006.
Serna ED. A Continuous Quality Improvement Project to Examine and Enhance Nurse's
Management of Tube Feedings. Presented at 9th Annual Madigan Research Day, Tacoma, WA,
April 2006.
Smith RD. An Evidence-Based Clinical Intervention Strategy to Reduce Falls: The Next
Generation. Presented at 9th Annual Madigan Research Day, Tacoma, WA, April 2006.
Tebbs JS. Decreasing Behavioral Restraint Use: A Workload Management Approach. Presented at
9th Annual Madigan Research Day, Tacoma, WA, April 2006.
Anesthesia Students, Department of Nursing
Andalis MA, Ribbing SK, Weston EM. The Effects of Chrysin, a Passiflora Incarnata Extract, on
Emergence Time from Anesthesia in Male Sprague-Dawley Rats after Intra-abdominal Surgery.
Presented at Annual Meeting, American Association of Nurse Anesthetists, Cleveland, OH, August
2006.
Bryant JV, Frondozo RR, King TL, Robinson JS. The Effects of St. John's Wort on Emergence
Time from General Anesthesia in Sprague-Dawley Rats (Rattus norvegicus) Undergoing
Abdominal Surgery. Presented at Annual Meeting, American Association of Nurse Anesthetists,
Cleveland, OH, August 2006.
Downs AM. Efficacy of Preoperative Valerian on Day of Surgery Anxiety. Presented at Phyllis J.
Verhonick Nursing Research Course, San Antonio, TX, May 2006.
Harm PS. Infection with Epidural Placement the Role of Asepsis in Reducing the Incidence of
Infections Complications. Presented at Washington Association of Nurse Anesthetists, Seattle,
WA, April 2006.
Kondrat PM. Current Perioperative Issues: Battlefield Lessons Learned. Presented at 8th Annual
TriService Perioperative Nursing Symposium, Washington, DC, March 2006.
Whitacre WC. Anesthesia in an Austere Environment: Afghanistan. Presented at Washington
Association of Nurse Anesthetists, Seattle, WA, April 2006.
Wulf PM, Long AL, Arredondo A, Petty LA, Marshall WB, Reilly M. The Laryngeal Mask Airway:
Comparison of Two Insertion Techniques and Waste Anesthetic Gas Leakage. Presented at
American Association of Nurse Anesthetists, November 2005.
Zwerling A, Fish D. Approaching the Patient with the Difficult Airway. Presented at Washington
Association of Nurse Anesthetists, Seattle, WA, April 2006.
25
Nursing Research Service, Department of Nursing
Argueta SJ. Nursing Workload Data Collection in the Post Anesthesia Care Unit. Presented at
Phyllis J. Verhonick Nursing Research Conference, San Antonio, TX, May 2006.
Hemman EA. Evaluation of the Semi-Annual Combat Medic Skills-Validation Test (SACMS-VT).
Presented at Tri-Service Nursing Research Conference: 13th Biennial Phyllis J. Verhonick
Nursing Research Course, San Antonio, TX, April 2006.
Hemman EA. Evaluation of the Semi-Annual Combat Medic Skills-Validation Test. Presented at
Tacoma General (Multicare), Tacoma, WA, June 2006.
Hopkins DL. Stress, Role Strain, Health & Military Career Aspiration in Junior Enlisted AirForce
Women With & Without Preschool Children. Presented at 14th Biennial Phyllis J. Verhonick
Nursing Research Course, San Antonio, TX, May 2006.
Ketz AK. The Experience and Management of Phantom Limb Pain in Patients with Traumatic
Amputation Resulting from Combat or Training Injury. Presented at Phyllis J. Verhonick Nursing
Research Conference, San Antonio, TX, May 2006.
Loan LA, Whitney D, Taylor JA. The Impact of Inpatient Physician Order Entry on Medication
Administration Errors Rates in the Neonatal Intermediate & Intensive Care Units. Presented at
Phyllis J. Verhonick Nursing Research Conference, San Antonio, TX, May 2006.
McCarthy MS, Simonson K, Sorensen D, Bamgartner B, Demars S. Perioperative
Immunonutrition for Head and Neck Cancer: A Feasibility Study. Presented at 14th Biennial
Phyllis J. Verhonick Nursing Research Course, San Antonio, TX, May 2006.
Schlicher ML. It's a Small World After All... Using Nanotechnology in Nursing & Medicine.
Presented at 2006 National Conference of the American Association of Critical Care Nurses,
Anaheim, CA, May 2006.
Smith RD. An Evidence-Based Clinical Intervention Strategy to Reduce Falls: The Next
Generation. Presented at 14th Biennial Phyllis J. Verhonick Nursing Research Course, San
Antonio, TX, May 2006.
Trego LL. Military Women's Thoughts on Menstruation and Menstrual Suppression During
Deployment. Presented at Pacific Nursing Research Conference, Honolulu, HI, February 2006.
Trego LL. Military Women's Thoughts on Menstruation and Menstrual Suppression During
Deployment. Presented at The Association of Women's Health, Obstetric, and Neonatal Nurses
(AWHONN), Baltimore, MD, June 2006.
Department of Obstetrics/Gynecology
Buchard E , Deering SH, Kuskowski LJ, Miller C, Driggers R. Incidental finding of angular
pregnancy delivered at 35 weeks for oligohydramnios: A case report and literature review.
Presented at 44th Annual Armed Forces District Meeting of the American College of Obstetricians
& Gynecologists, Seattle, WA, November 2005.
Burris AC. Resident Training in Assessment of the Sexual Assault Patient Utilizing Simulation.
Presented at 9th Annual Madigan Research Day, Tacoma, WA, April 2006.
Burris AC, Deering SH, Chinn M. Resident Training in Assessment of the Sexual Assault Patient
Utilizing Simulation. Presented at Council on Resident Eduation in OB/GYN (CREOG) and The
Association of Professors of Gynecology and Obstetrics (APGO) Annual Meeting, Orlando, FL,
March 2006.
Burris AC, Shields AD, Deering SH. Ovarian Vein Thrombosis in Early Pregnancy. Presented at
Annual ACOG Armed Forces District Meeting, Seattle, WA, November 2005.
26
Deering SH. Simulation Training for Postpartum Hemorrhage. Presented at Council on Residdent
Education in Obstetrics and Gynecology (CREOG) and The Association of Professors of
Gynecology and Obstetrics (APGO) Annual Meeting, Orlando, FL, March 2006.
Deering SH. Interactive Simulation Technologies in OB/GYN: Simulation Symposium. Presented
at 44th Annual Armed Forces District Meeting of the American College of Obstetricians &
Gynecologists, Seattle, WA, November 2005.
Gotkin JL. Progesterone Reduces Lipopolysaccharide Induced Interleukin- 6 Secretion in
Fetoplacental Arteries, Fractionated Cord Blood, and Maternal Mononuclear Cells. Presented at
9th Annual Madigan Research Day, Tacoma, WA, April 2006.
Gotkin JL, Flood SK , Deering SH. A new case of an old problem: A case report of sepsis resulting
from attempted self-termination. Presented at 44th Annual Armed Forces District Meeting of the
American College of Obstetricians & Gynecologists, Seattle, WA, November 2005.
Gotkin JL, McNutt PM, Celver JP, Shields AD, Wright JR, Hoeldtke NJ, Napolitano PG.
Progesterone Reduces Lipopolysaccharide Induced Inflammatory Cytokine Secretion in
Fetoplacental Arteries and Fractionated Cord Blood. Presented at 44th Annual Armed Forces
District Meeting of the American College of Obstetricians & Gynecologists, Seattle, WA, November
2005.
Gotkin JL, McNutt PM, Celver JP, Shields AD, Wright JR, Hoeldtke NJ, Napolitano PG.
Progesterone Reduces Lipopolysaccharide Induced Inflammatory Cytokine Secretion in
Fetoplacental Arteries and Fractionated Cord Blood. Presented at 44th Annual Armed Forces
District Meeting of the American College of Obstetricians & Gynecologists, Seattle, WA, November
2005.
Gotkin JL, McNutt PM, Celver JP, Shields AD, Wright JR , Hoeldtke NJ, Napolitano PG.
Progesterone Reduces Lipopolysaccharide Induced Inflammatory Cytokine Secretion in
Fetoplacental Arteries and Fractionated Cord Blood. Presented at 26th Annual Meeting of the
Society for Maternal-Fetal Medicine, Miami, FL, February 2006.
Gotkin JL, Shields A, Napolitano P, McNutt P, Celver J, Wright J. Progesterone Reduces
Lipopolysaccharide Induced Inflammatory Cytokine Secretion in Fetoplacental Arteries &
Fractionated Cord Blood. Presented at Society for Maternal Fetal Medicine Annual Meeting,
Miami, FL, February 2006.
Guidry BA, Napolitano PG. Screening for Depression at Postpartum Appointments. Presented at
44th Annual Armed Forces District Meeting of the American College of Obstetricians &
Gynecologists, Seattle, WA, November 2005.
Han JJ, Shen-Gunther J. Accuracy of Office Endometrial Biopsy: Comparison of Biopsy and
Hysterectomy Findings. Presented at Annual ACOG Armed Forces District Meeting, Seattle, WA,
October 2005.
Paonessa DJ. 17-Hydroxyprogesterone Caproate Reverses Thromboxane Induced Vaso¬
constriction of Fetal- Placental Arteries in the Ex Vivo Placental Cotyledon Model. Presented at 9th
Annual Madigan Research Day, Tacoma, WA, April 2006.
Paonessa DJ, Napolitano PG, Shields AD, Celver JP, Howard BC, Gotkin JL, Deering SH,
Hoeldtke NJ. The Effect of Cholic Acid on Placental Artery Perfusion Pressure in the Ex-Vivo
Placental Cotyledon Model. Presented at 44th Annual Armed Forces District Meeting of the
American College of Obstetricians & Gynecologists, Seattle, WA, November 2005.
Paonessa DJ, Shields AD, Celver JP, Howard BC, Gotkin JL, Hoeldtke NJ, Napolitano PG. 17-P
Hydroxyprogesterone Caproate Reverses Thromboxane Induced Vasoconstriction of Fetoplacental
Arteries in the Ex-Vivo Placental Cotyledon Model. Presented at 44th Annual Armed Forces
27
District Meeting of the American College of Obstetricians & Gynecologists, Seattle, WA, November
2005.
Saunders RD, Thomson SB, Shields AD. Renal Tubular Acidosis Presenting as Hypokalemia in
Pregnancy: A Case Report and Review of Literature. Presented at Annual ACOG Armed Forces
District Meeting, Seattle, WA, October 2005.
Sessions DC, Napolitano PG. Birth weight and macrosomia: Army versus Navy in the Puget
Sound. Presented at Annual ACOG Armed Forces District Meeting, Seattle, WA, October 2005.
Shen-Gunther J. Hereditary Cancer Genetic Testing: Referral Patterns and Outcomes. Presented
at Annual ACOG Armed Forces Distric Meeting, Seattle, WA, October 2005.
Shen-Gunther J. Extreme Drug Resistance Assay of Transitional Cell Ovarian Carcinoma.
Presented at Annual ACOG Armed Forces District Meeting, Seattle, WA, October 2005.
Shen-Gunther J. Does Early Treatment with Pegylated Liposomal Doxorubicin Improve Survival
Compared to Topotecan in Patients with Recurrent Ovarian Cancer? Presented at Society of
Gynecologic Oncologists 2006 Annual Meeting, Palmsprings, CA, March 2006.
Shields AD, Hill Dl. Management of Aplastic Anemia Diagnosed in Pregnancy: A Case Report and
Review of the Literature. Presented at 44th Annual Armed Forces District Meeting of the
American College of Obstetricians & Gynecologists, Seattle, WA, November 2005.
Temple ST, Shields AD. Fatal Congenital Cardiomyopathy in Type I Myotonic Dystrophy.
Presented at 44th Annual Armed Forces District Meeting of the American College of Obstetricians
& Gynecologists, Seattle, WA, November 2005.
Wakefield CL. GIST (Gastrointestinal Stromal Tumor) of the Vagina. Presented at Annual ACOG
Armed Forces District Meeting, Seattle, WA, October 2005.
Wilson KL, Lattu AL, Lucas W. Incisional Endometrioma Following Cesarean Delivery. Presented
at Annual ACOG Armed Forces District Meeting, Seattle, WA, October 2005.
You W, Driggers R, Bobo W, Deering SH. Treatment of anorexia nervosa in pregnancy: A case
report and review of the literature. Awarded Outstanding Poster. Presented at 44th Annual
Armed Forces District Meeting of the American College of Obstetricians & Gynecologists, Seattle,
WA, November 2005.
Zalucki CM. Paroxysmal Nocturnal Hemoglobinuria in Pregnancy. Presented at Annual ACOG
Armed Forces District Meeting, Seattle, WA, October 2005.
Department of Pathology
O'Brien KL. Three Unusual Histologic Variants of Fibrous Papule. Presented at International
Society of Dermatopathology 9th Joint Meeting, San Francisco, CA, March 2006.
O'Brien KL. Managing Patients with Rare Antibodies and Multiple Medical Issues is a Difficult
Problem Requiring a Team Approach. Presented at 9th Annual Madigan Research Day, Tacoma,
WA, April 2006.
Department of Pediatrics
Benton KB. A Case Report of an Isolated, Midline Facial Cutaneous Appendage: An Uncommon
Example of Disorganization in Humans. Presented at 9th Annual Madigan Research Day, Tacoma,
WA, April 2006.
Cornfeld RJ. Juvenile Arthritis Presenting as a Soft Tissue Mass. Presented at 9th Annual
Madigan Research Day, Tacoma, WA, April 2006.
28
Eigner DJ. Epstein-Barr Virus presenting as genital ulcers. Presented at Uniformed Services
Pediatric Seminar, Portsmouth, VA, March 2006.
Eigner DJ. Epstein-Barr Virus Infection Presenting as Genital Ulcers. Presented at 9th Annual
Madigan Research Day, Tacoma, WA, April 2006.
Fairchok MP. Pandemic Influenza - Not just for the birds. Presented at , Portsmouth, VA, March
2006.
Flake EM. Aortic Root Dilatation in a Patient with Overlapping Osteogenesis Imperfecta/Ehlers-
Danlos Syndrome Phenotype. Presented at 9th Annual Madigan Research Day, Tacoma, WA, April
2006.
Stephan MJ, Benton KB, Holm MT, Gries DM. Congenital Midline Facial Cutaneous Appendage:
Pathological Manifestations of Disorganization in Humans. Presented at XXVII David W. Smith
Workshop on Malformations and Morphogenesis, Lake Arrowhead, CA, September 2006.
Department of Preventive Medicine
Moores CA, Berke E, Cherutich P, Reed S. Elective Primary Cesarean Delivery in Washington
State: The Insurance Factor. Presented at 12th Annual Joint Conference on Health - Partnering
for a Healthier Tomorrow, February 2006.
Ross TW. Hearing Loss in the Military: The Results of Deployment to a Combat Environment.
Presented at 9th Annual Madigan Research Day, Tacoma, WA, April 2006.
Ross TW, Johnson R, Opheim G. Informatics and STD surveillance - a software application for
reporting and managing sexually transmitted diseases. Presented at Preventive Medicine 2006,
Reno, NV, February 2006.
Ross TW, Wiesen AR, Daniell W. Hearing Loss in the Military: The Results of Deployment to a
Combat Environment. Presented at National Occupational Research Agenda Symposium 2006,
Washington DC, April 2006.
Department of Psychology
Gahm GA. Post-Deployment Health Re-Assessment (PDHRA). Presented at Force Health
Protection 2006, Albuquerque, NM, August 2006.
Gahm GA, Meyer JG, Miller JL, Lucenko BA. The Soldier Wellness Assessment Pilot Program at
Ft. Lewis. Presented at Force Health Protection 2006, Albuquerque, NM, August 2006.
Lucenko BA. Screening for Mental Health Problems Following Deployment. Presented at Society
for Traumatic Stress Studies, Toronto, Canada, November 2005.
Peterson KA, Knauss LG. The Use of Prazosin in the Treatment of Combat-Related Nightmares in
Active Duty Soldiers. Presented at Albuquerque Convention Center, Albuquerque, NM, August
2006.
General Surgery Service, Department of Surgery
Arthurs ZM. The Impact of Hypothermia on Trauma Care at the 31st Combat Support Hospital in
Iraq. Presented at 9th Annual Madigan Research Day, Tacoma, WA, April 2006.
Arthurs ZM. RAS. Presented at Gary P. Wratten Army Surgical Symposium, Washington, DC,
May 2006.
29
Arthurs ZM, Cuadrado DG, Beekley AC, Grathwohl KW, Sebesta JA, Rush RM. The Impact of
Hypothermia on Trauma Care at the 31st Combat Support Hospital in Iraq. Presented at North
Pacific Surgical Association, Vancouver, BC, Canada, November 2005.
Beldowicz BC. Combat Vascular. Presented at Gary P. Wratten Army Surgical Symposium,
Washington, DC, May 2006.
Cronk DR, Houseworth TP, Herbert GS, Cuadrado DG, Azarow KS. Intestinal Fatty Acid Binding
Protein (I-FABP) for the Detection of Strangulated Mechanical Small Bowel Obstruction.
Presented at Pacific Coast Surgical Association 77th Annual Meeting, San Francisco, CA,
February 2006.
Cuadrado DG. 31st CSH Cause of Death. Presented at Gary P. Wratten Army Surgical
Symposium, Washington, DC, May 2006.
Eckert MJ, Azarow KS. Bronchoscopy in the Blast Injured Patient. Presented at Pacific Coast
Surgical Association 77th Annual Meeting, San Francisco, CA, February 2006.
Herbert GS. Intraperitoneal LPS Delivery in Mice Causes Multi-organ, Coordinated Modulation of
SDF-1? Production over a 72-Hour Period. Presented at 9th Annual Madigan Research Day,
Tacoma, WA, April 2006.
Herbert GS. SDF-1. Presented at Gary P. Wratten Army Surgical Symposium, Washington, DC,
May 2006.
Martin MJ. Pediatric Monitoring. Presented at San Antonio Trauma Symposium, San Antonio,
Tx, September 2006.
McGuigan RM, Spinella PC, Beekley A, Sebesta J, Perkins J, Grathwohl K, Azarow K. Pediatric
Trauma: Combat Support Hospital Experience in Iraq. Presented at American Pediatric Surgical
Association, South Carolina, May 2006.
Mullenix PS. MODS. Presented at Gary P. Wratten Army Surgical Symposium, Washington, DC,
May 2006.
Sohn VY. Combat Vascular. Presented at Gary P. Wratten Army Surgical Symposium,
Washington, DC, May 2006.
Sohn VY, Rush RM, Sebesta JA, Beekley AC, Gibson SO, Azarow KS, Koeller CA, Meyer JG.
From Buddy-aid to the Forward Surgical Team: The Madigan Model for Improving Trauma
Readiness of Brigade Combat Teams Fighting the Global War on Terror. Presented at 1st Annual
Academic Surgical Conference, San Diego, CA, February 2006.
Ophthalmology Service, Department of Surgery
Davis RW. LASIK Flap Stability in Ocular Trauma. Presented at 9th Annual Madigan Research
Day, Tacoma, WA, April 2006.
Frazier TC, Nelson ML. Case Series Late - Onset Corneal Haze > 10 months after Photo
Retractice Keratectomy (PBK) in Soldiers Deployed to Afghanistan. Presented at Annual
Symposium American Society, San Francisco, CA, March 2006.
Orthopedics Service, Department of Surgery
Gloystein DM. Developmental Dislocation of the Hip: A Long-Term Treatment Outcomes Study.
Presented at 9th Annual Madigan Research Day, Tacoma, WA, April 2006.
30
Gloystein DM, Grassbaugh JA, Arrington ED. PCL Tunnel Lengths, An Anatomic Study.
Presented at The American Academy of Orthopaedic Surgery, Annual Meeting, Chicago, IL, March
2005.
Guzzo JA, Herzog JP, Arrington E, Devine J. A Retrospective Review of Injuries Sustained During
OIF and OEF Treated at a Tertiary Military Medical Center. Presented at Washington State
Chapter of American College of Surgeons, Sun River, OR, June 2006.
Herzog JP, Arrington ED, Devine JG, Bluman EM. A Field Expedient Wound Vacuum System.
Presented at Washington State Chapter of American College of Surgeons, Sun River, OR, June
2006.
Ryan PM. The Role of the Triradiate Cartilage in Predicting Curve Progression in Adolescent
Idiopathic Scoliosis. Presented at 9th Annual Madigan Research Day, Tacoma, WA, April 2006.
Otolaryngology Service, Department of Surgery
Demars SM. Perioperative Immunonutrition in Head and Neck Cancer. Presented at 9th Annual
Madigan Research Day, Tacoma, WA, April 2006.
Demars SM, Harsha WJ, Crawford JV. Effects of Smoking on Rate of Post-Tonsillectomy
Hemorrhage. Presented at AAO-HNS Annual Meeting & Oto Expo, Toronto, CA, September 2006.
Poss JM. Post-Tympanostomy Swimming Precautions: A Physician Survey. Presented at AAO-
HNS Annual Meeting & Oto Expo, Toronto, Canada, September 2006.
Spear SA. Review of Thyroid Cancer Treatment Outcomes at a Major Medical Center from 1996-
2000. Presented at AAO-HNS Annual Meeting & Oto Expo, Toronto, Canada, September 2006.
Spear SA. Thyroid Cancer Treatment Outcomes at a Major Medical Center. Presented at 9th
Annual Madigan Research Day, Tacoma, WA, April 2006.
Urology Service, Department of Surgery
DeCastro BJ. Five Year Follow-up of Asymptomatic Men found to have Testicular Microlithiasis
in a Large Screening Study. Presented at 9th Annual Madigan Research Day, Tacoma, WA, April
2006.
Pugliese JM. The Epidemiology of Nephrolithiasis in Soldiers Returning from Operation Iraqi
Freedom. Presented at 9th Annual Madigan Research Day, Tacoma, WA, April 2006.
31
J. Publications
Hospital Dental Clinic
Viehweg TL. Melanoma of the Oral and Maxillofacial Region. Oral and Maxillofacial Surgical
Knowledge Update 2006.
Viehweg TL, Hudson JW. Pneumosinus dilitans of the Maxillary Sinuses, Bilaterally: A Case
Report. Journal of Oral and Maxillofacial Surgery 64(4): p. 726-30, 2006.
Department of Emergency Medicine
Billingsley RA, Keilman CG. Images in Emergency Medicine: Fournier's gangrene. Ann Emerg
Med 47(1): p. 11,21, 2006.
Blankenship RB. Six Steps to Buying Your First or Next PDA. ACEP News 2005.
Brandt AL, Tolson D. Missed abdominal ectopic pregnancy. J Emerg Med 30(2): p. 171-4, 2006.
Johnston GM, Denny MA, Howden J. Herpes Simplex Esophagitis in an Immunocompetent 20
year-old male. Resident and Staff Physician 2006.
Johnston GM, Wilson K, Harrison B. Images in Emergency Medicine: 21 year old female with
chronic constipation. Annals of Emergency Medicine 2006.
Murphy CS, Parsa T. Idiopathic Ovarian Vein Thrombosis a Rare Cause of Abdominal Pain. Am J
Emer Med 24(5): p. 636-7, 2006.
Nielson AS , Kang CS. Images in emergency Medicine. Chokehold Strangulation. Ann Emerg
Med 47(4): p. 327, 343, 2006.
Wedmore IS, McManus JG, Pusateri AE, Holcomb JB. A Special Report on the Chitosan-based
Hemostatic Dressing: Experience in Current Combat Operations. J Trauma 60(3): p. 655-8, 2006.
Wills BK, Mycyk MB, Mazor S, Kanter-Zell M, Brace L, Erickson T. Factitious Lithium Toxicity
Secondary to Lithium Heparin-Containing Blood Tubes. Journal of Medical Toxicology 2(2): p. 61-
3, 2006.
Department of Family Medicine
Aplund C, Webb C, Barkdull T. Neck and back pain in bicycling. Curr Sports Med Rep 4(5):
p. 271-4, 2005.
Edwards JA. Disposal of Unused and Expired Medications by Patients. NAPCRG 2005.
Edwards JA. Accuracy and Precision of Ear Canal Infrared Thermometers in a Simulated
Environment. NAPCRG 2005.
Jacoby G, Sams RW 2nd, Biagioli F. Clinical inquiries. Should people with a first-degree relative
who died from subarachnoid hemorrhage be screened for aneurysms? Journal of Family Practice
55(1): p. 59-60, 2006.
Junnila JL, Cartwright VW. Chronic musculoskeletal pain in children: part I. Initial evaluation.
Review. American Family Physician 74(1): p. 115-22, 2006.
Junnila JL, Cartwright VW. Chronic musculoskeletal pain in children: part II. Rheumatic causes.
Review. American Family Physician 74(2): p. 293-300, 2006.
32
Maurer DM, Fulton C, Doria M. Factors that influence the decision of military dependents to
decline smallpox vaccination during an outbreak. Mil Med. 171(4): p. 321-4, 2006.
Oh RC, Beresford SA, Lafferty WE. The Fish in Secondary Prevention of Heart Disease (FISH)
Survey -- Primary care physicians and predictors of omega-3 fatty acids prescribing behaviors. J
Am Board Fam Med 19(5): p. 459-67, 2006.
Seehusen DA, Baldwin LM, Runkle GP, Clark G. Are Family Physicians Appropriately Screening
for Postpartum Depression? Obstet Gynecol Surv 60(10): p. 630-1, 2005.
Stephens MB, Manning DA, Arnold-Canuso A, Haas DM. Maternal Shoe Size and Infant Birth
Weight: Correlation or Fiction? Am Board Family Medicine 19(4): p. 426-428, 2006.
Sullivan M, Sams RW 2nd, Jamieson B, Holt J. What is the best test to detect herpes in skin
lesions? Journal of Family Practice 55(4): p. 346 & 348, 2006.
Graduate Medical Eduction
Jorgensen JE, Roth BJ. Using Simulation in Medical Education. Insight 4(1): p. 12-3, 2006.
Roth BJ. Common Chief Resident Mistakes. APDIM: A Toolkit for Today's Chief Medical
Resident, 14th Edition 2006.
Health Outcomes Management Division
Bingham MO, Meyer JG, Birgenheier PS. Rebuilding a Future: A Soldier Readiness Case
Management Program. USAMEDD Journal 2005(7): p. 5-14, 2005.
Dermatology Service, Department of Medicine
Ferguson JW, Smith SB, Hirota TK. Photo Quiz: Tungiasis. Cutis 2006.
Infectious Disease Service, Department of Medicine
Ake JA, Erickson JC, Lowry KJ. Cerebral Aneurysmal Arteriopathy Associated with HIV
Infection in an adult. Clinical Infectious Diseases 43(5): p. e46-50, 2006.
Internal Medicine Service, Department of Medicine
Michaud E, Helwig M, Rossman M, Glorioso J, Salzman K. The Tactical Electronic Medical
Record: Medical Operations in the SBCT. US Army Medical Department Journal 2005.
Neurology Service, Department of Medicine
Erickson JC, Clapp LE, Ford G, Jabbari B. Somatosensory Auras in Refractory Temporal Lobe
Epilepsy. Epilepsia 47(1): p. 202-206, 2006.
Hohler AD, Flynn FG. Onset of Creutzfeldt- Jakob disease mimicking an acute cerebrovascular
event. Neurology 67(3): p. 538-9, 2006.
Joseph KR, Ney JP. Pediatric multiple sclerosis. Mayo Clin Proc 81(2): p. 151, 2006.
Ney JP, Riechers RG. Intramedullary Spinal Sarcoidosis: Clinical Improvement Reflected in T-
Lymphocyte Subpopulation ratios. . Spinal Cord 44(1): p. 49-51, 2006.
33
Department of Nursing
Kee CC, Foley BJ, Dudley W, Jennings BM, Minick P, Harvey SS. Nursing structure, processes,
and patient outcomes in army medical centers. West J Nurs Res 27(8): p. 1040-58, 2005.
Serna ED, McCarthy MS. Heads up to prevent aspiration during enteral feeding. Nursing 36(1):
p. 76-7, 2006.
Hopkins-Chadwick DL. The health readiness of junior enlisted military women: the social
determinants of health model and research questions. Mil Med 171(6): p. 544-9, 2006.
Prue-Owens KK. Use of Peripheral Venous Access Devices for Obtaining Blood Samples for
Measurement of Activated Partial Thromboplastin Times. Critical Care Nurse 26(#1): p. 30-38,
2006.
Stillsmoking KL. Simulation: Changing the Way Healthcare Professionals are Trained. Point of
View 45(1): p. 10, 2006.
Nursing Research Service, Department of Nursing
Jennings BM, Loan LA, Heiner SL, Hemman EA, Swanson KM. Soldiers' Experiences with
Military Health Care. Military Medicine 170(12): p. 999-1004, 2005.
Department of Obstetrics/Gynecology
Deering MA, Heller J, McGaha K, Heaton J, Satin AJ. Patients presenting with birth plans in a
military tertiary care hospital: a descriptive study of plans and outcomes. Mil Med 171(8): p. 778-
80, 2006.
Deering SH, Brown JA, Hodor J, Satin AJ. Simulation training and resident performance of
singleton vaginal breech delivery. Obstet Gynecol 107(1): p. 86-9, 2006.
Elliott DE, Patience TH, Boyd E, Hume RF, Calhound BC, Napolitano PG, Apodaca CC. Fetal
growth curves in an ethnically diverse military population: The AIUM accredited platform
experience. Mil Med 171(6): p. 508-511, 2006.
Paonessa DJ, Napolitano PG, Shields AD, Celver J, Howard BC, Gotkin JL, Deering S,
Hoeldtke NJ. The Effect of Cholic Acid on Placental Artery Perfusion Pressure in the Ex-Vivo
Placental Cotyledon Model. American Journal Obstet Gynecol 193: p. S173, 2006.
Thomson BA, Nielsen PE. Women's Health Care in Operation Iraqi Freedom: A survey of camps
with echelon I or II facilities. Military Med 171(3): p. 216-9, 2006.
VanBlaricom AL, Goff BA, Chinn M, Icasiano MM, Nielsen P, Mandel L. A New Curriculum for
Hysteroscopy Training as Demonstrated by an Objective Structured Assessment of Technical Skill
(OSATS). AM J Obstet Gynecol 193(5): p. 1856-65, 2005.
Woodman PJ, Swift SE, O'Boyle AL, Valley MT, Bland DR, Kahn MA, Schaffer JI. Prevalence of
Severe Pelvic Organ Prolapse in Relation to Job Description and Socioeconomic Status: A
Multicenter Cross-Sectional Study. Int Urogynecol J Pelvic Floor Dysfunct 17(4): p. 340-5, 2006.
Department of Pathology
34
Mahlen SD. Applications of Molecular Diagnostics Chapter. Textbook of Diagnostic Microbiology,
3rd Edition 2006.
O'Brien KL. Three Unusual Histologic Variants of Fibrous Papule. Am J Dermatopathol 28(3):
p. 234, 2006.
O'Brien KL, Chanpeaux AL. The Laboratory Officer on Duty as a Member of the Trauma Team.
Transfusion 46(9S): p. 178, 2006.
Weppler EH, Gaertner EM. Malignant Extragastrointestinal Stromal Tumor Presenting as A
Vaginal Mass: Report of an unusual Case with Literature Review. International Journal of
Gynecological Cancer 15(6): p. 1169-72, 2005.
Department of Pediatrics
Bondi SA, Gries D, Faucette K. Neonatal Euthanasia? Pediatrics 117(3): p. 983-4, 2006.
Braun LE, Tsuchida T, Spiegel H. Meningoencephalitis in a child complicated by myocarditis,
quadriparesis and respiratory failure. Pediatr Infect Dis J. 25(9): p. 853, 855-6, 2006.
Cartwright VW, Beitz L. Rheumatic Diseases and Their Treatments. Pediatric Critical Care
3(91): .
Davis BE, Shurtleff DB, Walker WO, Seidel KD, Duguay S. Acquisition of autonomy skills in
adolescents with myelomeningocele. Dev Med Child Neurol 48(4): p. 253-8, 2006.
Erdie-Lalena CR, Holm VA, Kelly PC, Frayo RS, Cummings DE. Gherlin Levels in Young
Children with Prader-Willi Syndrome. J Pediatrics 149(2): p. 199-204, 2006.
Harsha WT, Kalandarova E, McNutt PM, Irwin RG, Noel JM. Nutritional Supplementation with
TGFib, Glutamine and Short Chain Fatty Acids Minimizes Methotrexate-Induced Injury. J Pediatr
Gastroenterol Nutr 42(1): p. 53-8, 2006.
Maranich AM, Hamele M, Fairchok MP. Atlanto-Axial Subluxation: A Newly Reported
Trampolining Injury. Clinical Pediatrics (Phila) 45(5): p. 468-70, 2006.
Stephan MJ. A Tribute to Our Teacher, Dr. Judith Hall: A Child with the Trait of the Earl of
Shrewbury. Am J Med Genet A. 140(2): p. 156-9, 2006.
Szabo Z, Crepeau MW, Mitchell AL, Stephan MJ, Puntel RA, Loke YK, Kirk RC, Urban Z. Aortic
Aneurysmal Disease and Cutis Laxa Caused by Defects in the Elastin Gene. J Med Genet 43(3):
p. 255-258, 2006.
Walter EB, Neuzil KM, Zhu Y, Fairchok MP, Gagliano ME, Monto AS, Englund JA. Influenza
vaccine immunogenicity in 6- to 23-month-old children: are identical antigens necessary for
priming? Pediatrics 118(3): p. e570-8, 2006.
Physical Medicine & Rehabilitation Service
Greer MA, Essenberg EM, Weaver SH. A Review of 41 Upper Extremity War Injuries and the
Protective Gear Worn during Operation Enduring Freedom & Operation Iraqi Freedom. Military
Medicine 171(7): p. 595-7, 2006.
Department of Psychiatry
Doyle ME, Peterson KA. Re-entry and reintegration: Returning Home after combat. Psychiatr Q
76(4): p. 361-70, 2005.
35
Department of Radiology
Reidman DA, Balingit AG. Paradoxic technetium-99 methylene diphosphonate localization in
malignant mesothelioma. Clin Nucl Med 31(2): p. 71-3, 2006.
Ronsivalle JA, Statler JD, Venbrux AC, Arepally A. Intravascular bullet migration: A report of
two cases. Mil Med 170(12): p. 1044-7, 2005.
General Surgery Service, Department of Surgery
Arthurs ZM, Cuadrado DG, Beekley AC, Grathwohl KWA, Perkins J, Rush RM, Sebesta J. The
impact of hypothermia on trauma care at the 31st combat support hospital. Am J Surg 191(5):
p. 610-4, 2006.
Arthurs ZM, Kjorstad R, Mullenix P, Rush RM Jr, Sebesta J, Beekley A. The use of damage-
control principles for penetrating pelvic battlefield trauma. Am J Surg 191(5): p. 604-9, 2006.
Beekley AC. United States military surgical response to modern large-scale conflicts: the ongoing
evolution of a trauma system. Surg Clin North Am 86(3): p. 689-709, 2006.
Cronk DR, Houseworth TP, Cuadrado DG, Herbert GS, McNutt PM, Azarow KS. Intestinal fatty
acid binding protein (I-FABP) for the detection of strangulated mechanical small bowel
obstruction. Curr Surg 63(5): p. 322-5, 2006.
Eckert MJ, Clagett CL, Martin MJ, Azarow KS. Bronchoscopy in the blast injury patient. Arch
Surg 141(8): p. 806-9; discussion 810-1, 2006.
Martin MJ, FitzSullivan E, Salim A, Brown CV, Demetriades D, Long W. Discordance between
lactate and base deficit in the surgical intensive care unit: which one do you trust? Am J Surg.
191(5): p. 625-30, 2006.
Martin MJ, McDonald JM, Mullenix PS, Steele SR, Demetriades D. Operative management and
outcomes of traumatic lung resection. J Am Coll Surg 203(3): p. 336-44, 2006.
Martin RF, Rush RM. Chapter. Surgical Clinics of North America 86(3): p. 785, 2006.
McGuigan RM, Azarow KS. Congenital Chest Wall Defects. Surg Clinical North AM 86(2): p. 353-
70, 2006.
McGuigan RM, Mullenix PS, Vegunta R, Pearl R, Sawin R, Azarow KA. Splanchnic Perfusion
pressure: A better predictor of safe primary closure than intraabdominal pressure in neonatal
gastroschisis. J Pediatric Surg 41(5): p. 901-04, 2006.
Mullenix PS, Martin MJ, Steele SR, Hadro NC, Peterson RP, Anderson CA. Rapid High Volume
Population Screening for Three Major Risk Factors of Future Stroke: Phase I Results. Vase
Endovasc Surg 40(3): p. 177-87, 2005.
Mullenix PS, McDonald JM, Miller J, Needham CS. Modified Sternotomy to Minimize Infection
Risk in Patients with Prior Laryngectomy and Permanent Tracheostomy. J Card Surg 2006 21(4):
p. 403-6, 2006.
Mullenix PS, Steele SR, Andersen CA, Starnes BW, Salim A, Martin MJ. Limb salvage and
outcomes among patients with traumatic popliteal vascular injury: an analysis of the National
Trauma Data Bank. Journal of Vascular Surgery 44(1): p. 94-100, 2006.
Rush RM. Surgical support for low-intensity conflict, limited warfare, and special operations.
Surgical Clinics of North America 86(3): p. 727-52, 2006.
Steele SR, Madoff RD. Systematic review: The treatment of anal fissure. Aliment Pharmacol Ther
24(2): p. 247-57, 2006.
36
Steele SR, Martin MJ, Mullenix PS, Azarow KS, Andersen CA. The significance of incidental
thyroid abnormalities identified during carotid duplex ultrasonography. Archives of Surgery
141(10): p. 981-5, 2005.
Otolaryngology Service, Department of Surgery
Baumgartner BJ, Backous DD. Radiology quiz case 1. Postinflammatory fibrosis of the EAC
(medial canal fibrosis). Arch Otolaryngol Head Neck Surg 132(6): p. 690,692, 2006.
Baumgartner BJ, Peterson KL. A glottic wood chip presenting as chronic dysphonia: report of a
case and review of the literature. Arch Otolaryngol Head Neck Surg 132(1): p. 98-100, 2006.
Kelsch TA, Schaefer LA, Esquivel CR. Vestibular evoked myogenic potentials in young children:
test parameters and normative data. Laryngoscope 116(6): p. 895-900, 2006.
Urology Service, Department of Surgery
Pugliese JM, Peterson AC, Philbrick JH Jr, Allen RC Jr. Ureteral endometriosis in patients after
total abdominal hysterectomy: Presentation and diagnosis: A case series. Urology 67(3):
p. 622.el3-5, 2006.
Raj GV, Peterson AC, Webster GD. Outcomes Following Erosions of the Artificial Urinary
Sphincter. Urology 175: p. 2186-2190, 2006.
Vascular Surgery, Department of Surgery
Roukis TS. Determining the insertion site for retrograde intramedullary nail fixation of
tibiotalocalcaneal arthrodesis: A radiographic and intraoperative anatomical landmark analysis. J
Foot Ankle Surg 45(4): p. 227-34, 2006.
Roukis TS, Zgonis T. The management of acute Charcot fracture-dislocations with the Taylor's
spatial external fixation system. Clin Podiatr Med Surg 23(2): p. 467-83, viii, 2006.
Roukis TS, Zgonis T. Minimally invasive "pinless" external fixation for foot and ankle
reconstruction. . Orthopedics 29(3): p. 209-12, 2006.
Roukis TS, Zgonis T, Tiernan B. Autologoous platelet-rich plasma for wound and osseous healing:
A review of the literature and commercially available products. Adv Ther 23(2): p. 218-37, 2006.
Starnes BW. Peacekeeping and Stability Operations: A Military Surgeon's Perspective. Surgical
Clinics of North America 86(3): p. 753-63, 2006.
Starnes BW, Andersen CA, Ronsivalle JA, Stockmaster NR, Mullenix PS, Statler JD. Totally
percutaneous aortic aneurysm repair: Experience and prudence. J Vase Surg 43(2): p. 270-6, 2006.
Starnes BW, Arthurs ZM. Endovascular management of vascular trauma. Perspect Vase Surg
Endovasc Ther 18(2): p. 114-29, 2006.
Starnes BW, Beekley AC, Sebesta JA, Andersen CA, Rush RM Jr. Extremity vascular injuries on
the battlefield: Tips for surgeons eploying to war. J Trauma 60(2): p. 432-42, 2006.
37
K. Exempt Protocols approved in FY 2006 (no detailed summary sheet)
Number
PI
Dept/Serv
Protocol Title
206090
LaVan JT
FM
Identification of Health Factors Associated with Perceived
Quality of Life in an Aging Population
206017
Saguil AA
FM
Physician Perception of the Impact of a Morning Report
Educational Intervention
206046
Hopkins-Chadwick DL
Nurs
A Descriptive Study of Military Women's Information Needs
for Sexual Health Promotion
206007
Guidry BA
OB
Screening for Depression at Postpartum Appointments
206005
Han JJ
OB
Accuracy of Office Endometrial Biopsy: Comparison of
Biopsy and Hysterectomy Findings
206001
Sessions DC
OB
Birth Weight and Macrosomia: Army Versus Navy in the
Puget Sound
206003
Shen-Gunther J
OB
Cancer Genetic Testing: Referral Patterns and Outcomes
206065
Whitacre RM
Path
Post Approval Surveillance Study of Platelet Outcomes,
Release Tested
206060
Eichinger JK
Surg/Orth
Analysis of Failure Characteristics of Fixed Locking Plates
With and Without Screw- Hole Inserts: A Biomechanical
Study
206089
Schweinberger MH
Surg/V as
Foot Care Knowledge of Diabetic Patients in a Military
Medical Center
38
L. Detail Summary Sheets
Table of Contents for Detail Summary Sheets
Legend:
S = Status [0 - Ongoing, C - Completed, E - Expired, T - Terminated]
T = Protocol Type [A - Animal, B - Bench, C - Cancer, L - Local, M - Multicenter]
Prin. Invest. S T Title
#Protocol No.
DEPARTMENT OF ANESTHESIA & OPERATIVE SERVICES
Miller JP
#206121
0
M
Comparison of Direct Versus Indirect Laryngeal Views using the
Video Laryngoscope During Standard Intubation Procedures
Miller JP
#204010
C
L
Evaluation of the Combat Medic Skills Validation Test
DEPARTMENT OF CLINICAL INVESTIGATION
Bullock JM
#203122
E
A
Establishment of a Limb Regeneration Program Using
Notophthalmus viridescens (newt) as the Model Organism and the
Creation of a Transgenic N. viridescens Strain
Bullock JM
#206122
0
A
Profiling of Proteins Extracted from Tissue Taken from
Regenerating and Intact Notophthalmus viridescens Limbs Using
SELDI
Hartenstine MJ
#205031
0
L
Proteomic Analysis of Longitudinally-Collected Maternal Plasma
Samples: Establishing the 'Pregnancy Proteome'
McNutt PM
#205044
0
L
A Prospective Study of Pseudocholinesterase Activity in Patients
with Fibromyalgia, Chronic Pain, Pelvic Pain and Hernias
Merrill NL
#203092
E
A
Animal Tissue Use in Biomedical Research and Training
Merrill NL
#206109
0
A
Animal Tissue Use in Biomedical Research and Training
Merrill NL
#203076
T
A
Breeding Colony of Red-Spotted Newt (Notophthalmus viridescens)
Merrill NL
#206091
0
A
MAMC Rodent and Rabbit Quality Assurance and Sentinel Program
Merrill NL
#203075
T
A
Mouse (Mus Musculus) Breeding Protocol
HOSPITAL DENTAL CLINIC
Burgan SC
#203116
0
M
Host Response Gene 203014 in Military Populations
DEPARTMENT OF EMERGENCY MEDICINE
Cooper JL
#204087
T
L
A Prospective Study on the Effects of Ginkgo Biloba on Bleeding
Times
Denny MA
#206063
0
L
A Randomized Study of Capnography in Emergency Department
Procedural Sedation
Denny MA
#206050
T
L
Magnesium Sulfate for the Prevention of Etomidate Induced
Myoclonus in Emergency Department Procedural Sedation
39
Prin. Invest. S T Title
#Protocol No.
Johnston GM
#206028
C L Application of the Wells Criteria to determine Pretest Probability of
Pulmonary Embolism: A Retrospective Review of the practices of
the Madigan Army Medical Center Department of Emergency
Medicine
Nielson AS
#206059
0 L Causes and consequences of patients who left a busy Army Medical
Center Emergency Department prior to evaluation by a qualified
health care provider
Younggren BN
#206078
O A Emergency Medicine/Combat Trauma Management Training Using
Animal Models (Domestic Goat/ Capra hircus, Pig/Sus scrofa)
DEPARTMENT OF FAMILY MEDICINE
Clark GW
#205133
O L Prevalence of Hypertension in Active Duty Service Members
Crosland T
#205124
Flynn DM
#204117
Flynn DM
#206105
Kelly KM
#205130
Kimmer SL
#206019
O L Racial Differences in Health Outcomes for Adults with Diabetes in a
Military Setting
O L Impact of the Sole Prescriber Program on use of Opioid Medications
and Quality of Life
O L Implementation of an Office-Based Screening Tool to Improve
Adherence with Recommended Preventive Services in Primary Care
O L Use of Pedometers Among Healthcare Providers in a Large Military
Family Medicine Department
C L Pediatric Obesity in a Military Family Medicine Clinic
Maurer DM
#206048
Pflipsen MC
#205025
Rosen IM
#206067
O L A Randomized, Controlled Trial of Manual/Manipulative Therapy
for Acute Low Back Pain in Active Duty Military Personnel: A Pilot
Study
C L Prevalence of Vitamin B12 Deficiency in the Type 2 Diabetic
Population
C L Determinants of Military Medical Student Interest in Family
Medicine
Saguil AA
#205103
Sams RW
#206104
C M The Role of Evidence and Other Determinants in Resident
Discussions of Spirituality with Patients
O L Implementing a Medical Ethics Curriculum in a Family Medicine
Residency: Assessment of Need, Description of the Process, and
Evaluation of Effectiveness
Short MW
#205132
Short MW
#205131
Short MW
#206080
C L Colonoscopy by a Family Physician: A Case Series Demonstrating
Healthcare Savings
C L Esophagogastroduodenoscopy by a Family Physician: A Case Series
Demonstrating Healthcare Savings
O L Predicting Intern Performance using an Objective Structured
Clinical Examination
GRADUATE MEDICAL EDUCATION
Boden JH O L
#205090
Attitudes and Perceptions of Refractive Surgery Among ROTC
Cadets Presenting for a Flight Physical and Self-Reported Barriers
Towards Having Refractive Surgery to Correct Visual Acuity and
Becoming Medically Qualified for Army Aviation
HEALTH OUTCOMES MANAGEMENT DIVISION
Meyer JG O L The Deployment of Physical Therapy for Combat: A Description of
#205108 the Process and Outcomes
40
Prin. Invest.
#Protocol No.
S T Title
CARDIOLOGY SERVICE, DEPARTMENT OF MEDICINE
Schachter DT 0 L CardioSEAL Septal Occlusion System (HUD)
#202300
Schachter DT 0 L Jostent Coronary Stent Graft (HUD)
#201300
HEMATOLOGY/ONCOLOGY SERVICE, DEPARTMENT OF MEDICINE
Brown TA O S CTSU E5202: A Randomized Phase III Study Comparing 5-FU,
#206113 Leucovorin and Oxaliplatin versus 5-FU, Leucovorin, Oxaliplatin
and Bevacizumab in Patients with Stage II Colon Cancer at High
Risk for Recurrence to Determine Prospectively the Prognostic
Value of Molecular Markers
Daniels JT
#206023
Daniels JT
#205094
O M A Multi-Center, Randomized, Phase 3 Study of Iodine 1-131
Tositumomab Therapeutic Regimen Versus Ibritumomab Tiuxetan
Therapeutic Regimen for Subjects with Relapsed or Transformed
Follicular Non-Hodgkin's Lymphoma
T M A Randomized, Open-Label Trial Comparing Two Avastin™
(Bevacizumab)-Based Treatment Regimens For The First-Line
Treatment Of Metastatic Colorectal Cancer
Daniels JT
#206103
T M Phase 3, Multicenter, Multi-National, Open-Label Study to Evaluate
the Safety and Efficacy of Alfimeprase in Subjects with Occluded
Central Venous Access Devices
Daniels JT
#205007
Daniels JT
#89080
Daniels JT
#90027
S M PSOC 2003: A Phase II Study Evaluating the Efficacy of
Gemcitabine, Carboplatin, Dexamethasone and Rituximab for
Previously Treated Lymphoid Malignancies, UW Protocol Number
LYM.03.01
T S SWOG 8814 (ECOG 4188, NCCTG 883051): Phase III Comparison of
Adjuvant Chemoendocrine Therapy with CAF and Concurrent or
Delayed Tamoxifen to Tamoxifen Alone in Postmenopausal Patients
with Breast Cancer Having Involved Axillary Nodes and Positive
Hormone Receptors
O S SWOG 8851 (EST 5811, INT-0101): Phase III Comparison of
Combination Chemotherapy (CAF) and Chemohormonal Therapy
(CAF + Zoladex or CAF + Zoladex + Tamoxifen) in Premenopausal
Women with Axillary Node-Positive, Receptor- Positive Breast
Cancer
Daniels JT
#90029
T S SWOG 8897 (EST-2188, CALGB-8897, INT-0101): Phase III
Comparison of Adjuvant Chemotherapy With or Without Endocrine
Therapy in High-Risk, Node Negative Breast Cancer Patients, and a
Natural History Follow-up Study in Low-Risk, Node Negative
Patients
Daniels JT
#90056
Daniels JT
#97096
C S SWOG 8997 (ECOG 3887): Phase III Chemotherapy of Disseminated
Advanced Stage Testicular Cancer with Cisplatin Plus Etoposide
with Either Bleomycin or Ifosfamide
O S SWOG 9059 (E1392, INT-0126): Phase III Comparison of Standard
Radiotherapy versus Radiotherapy plus Simultaneous Cisplatin,
versus, split- Course Radiotherapy plus Simultaneous Cisplatin and
5-Fluorouracil, in Patients with Unresectable Squamous Cell
Carcinoma of the Head and Neck
41
Prin. Invest. S T Title
#Protocol No.
Daniels JT
#93032
Daniels JT
#93097
Daniels JT
#93136
Daniels JT
#93166
Daniels JT
#94170
Daniels JT
#95003
Daniels JT
#95093
Daniels JT
#94163
Daniels JT
#96095
Daniels JT
#96118
Daniels JT
#98112
Daniels JT
#99014
Daniels JT
#200036
Daniels JT
#99071
0 S SWOG 9061 (EST-2190, INT 0121): A Phase III Study of
Conventional Adjuvant Chemotherapy vs High Dose Chemotherapy
and Autologous Bone Marrow Transplantation or Stem Cell
Transplantation as Adjuvant Intensification Therapy Following
Conventional Adjuvant Chemotherapy in Patients with Stage II and
III Breast Cancer at High Risk of Recurrence
O S SWOG 9205: Central Prostate Cancer Serum Repository Protocol
O S SWOG 9221, MDACC ID 91-025, INT- 191-001: Phase III Double-
Blind Randomized Trial of 13-Cis Retinoic Acid (13-cRA) to Prevent
Second Primary Tumors (SPTs) in Stage I Non-Small Cell Lung
Cancer
O S SWOG 9303: Phase III Study of Radiation Therapy, Levamisole, and
5-Fluorouracil versus 5-Fluorouracil and Levamisole in Selected
Patients With Completely Resected Colon Cancer
T S SWOG 9313: Phase III Comparison of Adjuvant Chemotherapy With
High-Dose Cyclophosphamide + Doxorubicin vs Sequential
Doxorubicin Followed by Cyclophosphamide in High-Risk Breast
Cancer Patients with 0-3 Positive Nodes
O S SWOG 9401: A Controlled Phase III Evaluation of 5-FU Combined
with Levamisole and Leucovorin as Surgical Adjuvant Treatment
Following Total Gross Resection of Metastatic Colorectal Cancer
O S SWOG 9402: Phase III Intergroup Randomized Comparison of
Radiation Alone vs Pre-Radiation Chemotherapy for Pure and Mixed
Anaplastic Oligodendrogliomas
O S SWOG 9410 (INT 0148): Doxorubicin Dose Escalation, With or
Without Taxol, As Part of the CA Adjuvant Chemotherapy Regimen
for Node Positive Breast Cancer: A Phase III Intergroup Study
O S SWOG 9514: Phase III Double-Blind, Placebo-Controlled,
Prospective Randomized Comparison of Adjuvant Therapy with
Tamoxifen vs. Tamoxifen & Fenretinide in Postmenopausal Women
with Involved Axillary Lymph Nodes and Positive Receptors,
Intergroup
O S SWOG 9515: Phase III Intergroup Trial of Surgery Followed by (1)
Radiotherapy vs. (2) Radiochemotherapy for Resectable High Risk
Squamous Cell Carcinoma of the Head and Neck
O S SWOG C9581: Phase III Randomized Study of Adjuvant
Immunotherapy with Monoclonal Antibody 17-lA Versus No
Adjuvant Therapy Following Resection for Stage II (Modified Astler-
Coller B2) Adenocarcinoma
O S SWOG C9741: A Randomized Phase III Trial of Sequential
Chemotherapy Using Doxorubicin, Paclitaxel, and
Cyclophosphamide, or Concurrent Doxorubicin and
Cyclophosphamide Followed by Paclitaxel at 14 or 21 Day Intervals
in Women with Node Positive Stage II/IIIA Breast Cancer
O S SWOG E1199: A Phase III Study of Doxorubicin- Cyclophosphamide
Therapy Followed by Paclitaxel or Docetaxel Given Weekly or Every
3 Weeks in Patients with Axillary Node-Positive Breast Cancer
O S SWOG E2197: Phase III Study of Adriamycin/Taxotere vs.
Adriamycin/Cytoxan for the Adjuvant Treatment of Node Positive or
High Risk Node Negative Breast Cancer
42
Prin. Invest. S T Title
#Protocol No.
Daniels JT
#204066
Daniels JT
#200040
Daniels JT
#202010
Daniels JT
#202012
Daniels JT
#97070
Daniels JT
#99040
Daniels JT
#200120
Daniels JT
#201136
Daniels JT
#201137
Daniels JT
#203084
Daniels JT
#204052
Daniels JT
#204123
0 S SWOG E2496 Randomized Phase III Trial of ABVD Versus Stanford
V +/- Radiation Therapy in Locally Extensive and Advanced Stage
Hodgkin's Disease With 0-2 Risk Factors
O S SWOG E4494: Phase III Trial of CHOP versus CHOP and Chimeric
Anti-CD20 Monoclonal Antibody (IDEC-C2B8) in Older Patients
with Diffuse Mixed, Diffuse Large Cell and Immunoblastic Large
Cell Histology Non-Hodgkin's Lymphoma
O S SWOG E5597: Phase III Chemoprevention Trial of Selenium
Supplementation in Persons with Resected Stage I Non- Small Cell
Lung Cancer
O S SWOG GO 182: A Phase III Randomized Trial of Paclitaxel and
Carboplatin Versus Triplet or Sequential Doublet Combinations in
Patients with Epithelial Ovarian or Primary Peritoneal Carcinoma
O S SWOG JBR. 10 (NCIC CTG BR. 10): A Phase III Prospective
Randomized Study of Adjuvant Chemotherapy with Vinorelbine and
Cisplatin in Completely Resected Non-small Cell Lung Cancer with
Companion Tumour
O S SWOG JMA. 17: A Phase III Randomized Double-Blinded Study of
Letrozole Versus Placebo in Women with Primary Breast Cancer
Completing Five or More Years of Adjuvant Tamoxifen
O S SWOG N9831: Phase III Trial of Doxorubicin and
Cyclophosphamide (AC) Followed by Weekly Paclitaxel With or
Without Trastuzumab as Adjuvant Treatment for Women with
HER-2 Over-expressing or Amplified Node Positive or High-Risk
Node Negative Breast Cancer (an Intergroup Study)
C S SWOG S0009: A Phase II Evaluation of Neoadjuvant
Chemotherapy, Interval Debulking Followed by Intraperitoneal
Chemotherapy in Women with Stage III and IV Epithelial Ovarian
Cancer, Fallopian Tube Cancer or Primary Peritoneal Cancer
O S SWOG S0012: A Comparative Randomized Study of Standard
Doxorubicin and Cyclophosphamide Followed by Weekly Paclitaxel
Vs. Weekly Doxorubicin and Daily Oral Cyclophosphamide Plus G-
CSF Followed by Weekly Paclitaxel as Neoadjuvant Therapy for
Inflammatory and Locally Advanced Breast Cancer
O S SWOG S0016, A Phase III Trial of CHOP + Rituximab vs. CHOP +
Iodine-131-Labeled Monoclonal Anti-Bl Antibody (Tositumomab) for
Treatment of Newly Diagnosed Follicular Non-Hodgkin's
Lymphomas
C S SWOG S0023, A Phase III Trial of Cisplatin/Etoposide/Radiotherapy
with Consolidation Docetaxel Followed by Maintenance Therapy
with ZD 1839 or Placebo in Patients With Inoperable Locally
Advanced Stage III Non-Small Cell Lung Cancer
O S SWOG S0106, A Phase III Study of the Addition of Gemtuzumab
Ozogamicin (Mylotarg®) Induction Therapy Versus Standard
Induction With Daunomycin and Cytosine Arabinoside Followed by
Consolidation and Subsequent Randomization to Post-Consolidation
Therapy With Gemtuzumab Ozogamicin (Mylotarg®) or No
Additional Therapy for Patients Under Age 56 With Previously
Untreated DeNovo Acute Myeloid Leukemia (AML)
43
Prin. Invest.
#Protocol No.
Daniels JT
#204034
Daniels JT
#204094
Daniels JT
#204064
Daniels JT
#206068
Daniels JT
#91094
Daniels JT
#99019
Daniels JT
#205035
Daniels JT
#200084
Daniels JT
#202074
McCune DE
#204073
McCune DE
#205093
McCune DE
#206014
McCune DE
#205016
McCune DE
#205087
McCune DE
#205070
S T Title
0 S SWOG S0221, Phase III Trial of Continuous Schedule AC + G Vs. Q
2 Week Schedule AC, Followed by Paclitaxel Given Either Every 2
Weeks or Weekly for 12 Weeks as Post-Operative Adjuvant Therapy
in Node-Positive or High-Risk Node-Negative Breast Cancer
O S SWOG S0226, Phase III Randomized Trial of Anastrozole Versus
Anastrozole and Fulvestrant as First Line Therapy for Post
Menopausal Women With Metastatic Breast Cancer
O S SWOG S0230, Phase III Trial of LHRH Analog Administration
During Chemotherapy to Reduce Ovarian Failure Following
Chemotherapy in Early Stage, Hormone- Receptor Negative Breast
Cancer
O S SWOG S0520: Phase II Study of PXD101 (NSC-726630) in Relapsed
and Refractory Aggressive B-Cell Lymphomas
O S SWOG S9007 (ECOG S9007), Cytogenetic Studies in Leukemia
Patients
O S SWOG S9808: Long-Term Follow-Up Protocol: An Administrative
Tool
O S SWOG S9910 Leukemia Centralized Reference Laboratories and
Tissue Repositories, Ancillary
O S SWOG S9921: Adjuvant Androgen Deprivation versus Mitoxantrone
plus Prednisone plus Androgen Deprivation in Selected High Risk
Prostate Cancer Patients Following Radical Prostatectomy, Phase
III
O S SWOG S9925 Lung Cancer Specimen Repository Protocol, Ancillary
O M A Multicenter, Randomized, Phase III Study of Rituximab versus
Iodine I 131 Tositumomab Therapeutic Regimen for Patients with
Relapsed Follicular Non-Hodgkin's Lymphoma, Protocol CCBX001-
049
O M A Phase 3, Double-Blind, Placebo-Controlled Study of Maintenance
Premetrexed plus Best Supportive Care versus Best Supportive
Care Immediately Following Induction Treatment for Advanced
Non-Small Cell Lung Cancer AND COMPANION STUDY
Companion Translational Research Protocol
O M A Phase I/II Trial of Zometa in Patients with Monoclonal
Gammopathy of Undetermined Significance (MGUS)
T M A Phase II Multicenter, Randomized, Double-blind, Placebo-
controlled Dose-Ranging, Parallel Group Study of the Safety and
Efficacy of the Oral Neurokinin- 1 Receptor Antagonist, GW679769,
When Administered as 50mg, lOOmg, and 150mg Oral Tablets in
Combination with Ondansetron Hydrochloride and Dexamethasone
for the Prevention of Chemotherapy-Induced Nausea and Vomiting
in Cancer Subjects Receiving Moderately Emetogenic Chemotherapy
S M A Phase II, Open Label, Multi-center Study of EP2 101 Therapeutic
Vaccine in Patients with Stage Illb, Stage IV, or Recurrent Non-
Small Cell Lung Cancer (NSCLC)
O M A Phase II Study Using Alemtuzumab Combined with Fludarabine
for the Treatment of Relapsed/Refractory B-cell Chronic
Lymphocytic Leukemia (B-CLL)
44
Prin. Invest.
#Protocol No.
McCune DE
#206126
McCune DE
#204114
McCune DE
#204006
McCune DE
#204044
McCune DE
#204096
McCune DE
#202083
McCune DE
#204107
McCune DE
#202114
McCune DE
#202089
McCune DE
#204124
McCune DE
#202088
McCune DE
#204072
S T Title
0 L A Phase II Trial of Imatinib (Gleevec) Plus Gemcitabine In Patients
With Ovarian Carcinoma Who Have Failed At Least One Prior
Chemotherapy
O M A Phase II Trial of Weekly Docetaxel plus Every 3-Week
Carboplatin in Patients with Stage IIIB/IV Non-small Cell Lung
Cancer, Protocol GIA 12156
T M A Phase III, Randomized, Double-blinded Efficacy and Safety Study
of Three Doses of TAS-108 Administrated Orally in Postmenopausal
Patients with Locally Advanced or Locally Recurrent Inoperable or
Progressive Metastatic Breast Carcinoma Following Standard First
Line Endocrine Therapy, Protocol Number TAS 108-0004
O M A Phase III Study of Delayed vs. Immediate Second-line Therapy
with Docetaxel after Gemcitabine + Carboplatin in Advanced Non-
Small Cell Lung Cancer, Protocol Number B9E-US-S245
CM A Randomized, Open-Label Study of PROCRIT® (Epoetin Alfa)
Initiated at 40,000 Units Every Week Versus 80,000 Units Every
Two Weeks In Anemic Patients With Cancer Receiving
Chemotherapy, Protocol PR03-27-064
O M A Randomized Phase III Trial of Gemzar versus Doxil with
Crossover Treatment Option for Patients with Platinum-Resistant
Ovarian, Fallopian Tube or Primary Peritoneal Cancer Undergoing
Second or Third-Line Chemotherapy, Protocol Number: B9E-US-
S301
S S CTSU ACOSOG-Z9001, A Phase III Randomized Double-blind Study
of Adjuvant STI571 (Gleevec™) Versus Placebo in Patients
Following the Resection of Primary Gastrointestinal Stromal Tumor
(GIST)
O S CTSU CALGB 40101, Cyclophosphamide and Doxorubicin (CA) (4
VS 6 Cycles) versus Paclitaxel (4 VS 6 Cycles) as Adjuvant Therapy
for Women with 0-3 Positive Axillary Lymph Nodes: A 2X2 Factorial
Phase III Randomized Study
O S CTSU CALGB 49907, A Randomized Trial of Adjuvant
Chemotherapy With Standard Regimens, Cyclophosphamide,
Methotrexate and Fluorouracil - (CMF) or Doxorubicin and
Cyclophosphamide - (AC), Versus Capecitabine in Women 65 Years
and Older with Node Positive or Node Negative Breast Cancer
C S CTSU CALGB 80303, A Randomized Phase III Trial of Gemcitabine
plus Bevacizumab (NSC #704865 IND #7921) Versus Gemcitabine
plus Placebo in Patients With Advanced Pancreatic Cancer
O S CTSU E1A00 A Randomized Phase III Trial of Thalidomide (NSC
#66847) Plus Dexamethasone versus Dexamethasone in Newly
Diagnosed Multiple Myeloma
C S CTSU E3201 Intergroup Randomized Phase III Study of
Postoperative Irinotecan, 5 -Fluorouracil and Leucovorin vs
Oxaliplatin, 5 -Fluorouracil and Leucovorin vs 5 -Fluorouracil and
Leucovorin for Patients with Stage II or III Rectal Cancer Receiving
Either Preoperative Radiation and 5 -Fluorouracil or Postoperative
Radiation and 5 -Fluorouracil
45
Prin. Invest.
#Protocol No.
S T Title
McCune DE
#204043
McCune DE
#204035
McCune DE
#205071
McCune DE
#202043
McCune DE
#206112
McCune DE
#206054
McCune DE
#206073
McCune DE
#204008
McCune DE
#206084
McCune DE
#204080
McCune DE
#202107
McCune DE
#206055
McCune DE
#206013
0 S CTSU IBCSG Trial 25-02, Tamoxifen and Exemestane Trial (TEXT),
A Phase III Trial Evaluating the Role of Exemestane Plus GnRH
Analogue as Adjuvant Therapy for Premenopausal Women with
Endocrine Responsive Breast Cancer
O S CTSU NCIC CTG MA.27, A Randomized Phase III Trial of
Exemestane Versus Anastrozole in Postmenopausal Women With
Receptor Positive Primary Breast Cancer
T S CTSU NSABP 80101 Phase III Intergroup Trial of Adjuvant
Chemoradiation after Resection of Gastric or Gastroesophageal
Adenocarcinoma
O S CTSU RTOG 98-04: Phase III Trial of Observation +/- Tamoxifen vs.
RT +/- Tamoxifen for Good Risk Duct Carcinoma In-Situ (DCIS) of
the Female Breast
O G CTSU/GOG 0218 A Phase III Trial of Carboplatin and Paclitaxel
Plus Placebo Versus Carboplatin and Paclitaxel Plus Concurrent
Bevacizumab (NSC #704865, IND #7921) Followed By Placebo,
Versus Carboplatin and Paclitaxel Plus Concurrent and Extended
Bevacizumab, In Women With Newly Diagnosed, Previously
Untreated, Suboptimal Advanced Stage Epithelial Ovarian and
Primary Peritoneal Cancer
O M NSABP B-38 A Phase III Adjuvant Trial Comparing Three
Chemotherapy Regimens in Women with Node-Positive Breast
Cancer: Docetaxel/Doxorubicin/Cyclophosphamide (TAC); Dose-
Dense (DD) Doxorubicin/Cyclophosphamide Followed by DD
Paclitaxel (DD AC-P); DD Doxorubicin/Cyclophosphamide Followed
by DD Paclitaxel Plus Gemcitabine (DD AC-PG)
O M Phase 1/2 study of ZK-Epothilone (ZK-Epo; ZK 219477) in
combination with carboplatin in patients with platinum-sensitive,
recurrent ovarian cancer
O M Phase II Trial of ONTAK® in Refractory or Relapsed Advanced Non¬
small Cell Lung Cancer (NSCLC)
O M Pilot Study to Evaluate the Safety and Efficacy of PROCRIT
(Epoetin alfa) 80,000 Units Once Every Four Weeks (Q4W) vs.
40,000 Units Once Every Two Weeks (Q2W) in Cancer Patients with
Non-Chemotherapy Anemia
O M Protocol U2963n: The National Lymphocare Study: An
Observational Study of Treatment, Outcomes, and Prognosis in
Patients With Follicular Non-Hodgkin's Lymphoma
C L Randomized Study of Docetaxel Versus Docetaxel Plus
GenasenseTM (G3139; Bcl-2 Antisense Oligonucleotide) in Patients
with Previously Treated Non- Small Cell Lung Cancer, No. N304
O S SWOG S0424: Molecular Epidemiology Case-Series Study of Non-
Small Cell Lung Cancer in Smoking and Non-Smoking Women and
Men
O S SWOG S0435 A Phase II Trial of BAY 43-9006 (SNC-724772) in
Patients with Platinum-Treated Extensive Stage Small Cell Lung
Cancer
46
Prin. Invest.
#Protocol No.
Title
S T
Mysliwiec AG
#205036
Mysliwiec AG
#206025
0 S CTSU NSABP C-08, A Phase III Clinical Trial Comparing Infusional
5-Fluorouracil (5-FU), Leucovorin, And Oxaliplatin (mFOLFOX6)
Every Two Weeks With Bevacizumab To The Same Regimen
Without Bevacizumab For The Treatment Of Patients With
Resected Stages II And III Carcinoma of the Colon
T M RegistHER: An Observational Cohort Study of Patients with HER2-
Positive Metastatic Breast Cancer
Ramsdell MJ
#204082
O L Evaluating Cognitive Function in Women Receiving Chemotherapy
for Newly Diagnosed Breast Cancer
INTERNAL MEDICINE SERVICE, DEPARTMENT OF MEDICINE
Avalos C
#205046
O L The Effect of Blood Transfusion on Serum Ferritin and Iron
Bauler KC
#205123
DeHaan PJ
#205039
Evans NR
#206119
Fischer CJ
#206064
O L Current Use and Complications of Peripherally Inserted Central
Catheters (PICC): A Retrospective Study
O L Management of Parapneumonic Effusions: Does Following
Pneumonia Treatment Guidelines Affect Outcome? A Retrospective
Study
O L Urinary Markers of Renal Injury and N- Acetylcysteine Efficacy
(URINE)
C L Does Participation in a Subspecialty Elective Rotation Improve the
Respective American Board of Internal Medicine Subspecialty
Score?
Kiley CA
#205104
Kwon HP
#206087
C L Appropriate Use of CTPA in the Evaluation of Pulmonary Embolism
- An Examination of Hospital-Wide Referral Practices
O L Hemoptysis in Young Adults
Kwon HP
#206069
Mount GR
#205038
Short PA
#202048
O L The Effects of Nighttime Low Dose Aspirin on Ambulatory Blood
Pressure Testing in Treated Hypertensive Patients
T L Effect of A Single Intra-articular Steroid Injection on Serum
Fructosamine Levels in Patients with Type 2 Diabetes Mellitus
O M A Multinational, Randomized, Double-blind, Placebo-controlled,
Forced-titration, 2X2 Factorial Design Study of the Efficacy and
Safety of Long Term Administration of Nateglinide and Valsartan in
the Prevention of Diabetes and Cardiovascular Outcomes in Subjects
with Impaired Glucose Tolerance (IGT), Protocol No. CDJN608
B2302
Short PA
#204045
Wang JY
#205004
O M A Prospective, multinational, multicenter, double-blind, randomized,
active-controlled trial to compare the effects of Lotrel
(amlodipine/benazepril) to benazepril and hydrochlorothiazide
combined on the reduction of cardiovascular morbidity and mortality
in patients with high risk hypertension, Protocol No. CCIB002I2301:
ACCOMPLISH (Avoiding Cardiovascular Events through
COMbination Therapy in Patients Living with Systolic
Hypertension)
C L Efficacy of Iron in Restless Legs Syndrome (RLS) Patients With
Low-Normal Ferritin: A Randomized, Double-Blind, Placebo
Controlled Study
NEPHROLOGY SERVICE, DEPARTMENT OF MEDICINE
Lee JY C L Does High Resistive Index by Doppler Ultrasonography Predict
#205121 Small Kidney Sizes?
47
Prin. Invest. S T Title
#Protocol No.
NEUROLOGY SERVICE, DEPARTMENT OF MEDICINE
Erickson JC
#204062
Erickson JC
#203048
Erickson JC
#206075
Erickson JC
#203097
Erickson JC
#205107
Erickson JC
#205118
Erickson JC
#205115
O L A Randomized Trial of a Migraine Management Seminar in the
Treatment of Migraines
O L A Randomized Trial of B Vitamins for Alzheimer's Disease
O L Association Between Migraine and Psychiatric Conditions In
Soldiers Returning from Combat
O M CLOSURE I Trial: A Prospective, Multicenter, Randomized,
Controlled Trial to Evaluate the Safety and Efficacy of the
STARFlex Septal Closure System Versus Best Medical Therapy in
Patients with a Stroke and/or Transient Ischemic Attack Due to a
Presumed Paradoxical Embolism Through a Patent Foramen Ovale
C L Diagnosis and Treatment of Migraines in U.S. Army Soldiers
O L Prevalence and Impact of Migraine Among Deployed Soldiers
O M Study of Acute Viprinex™ for Emergency Stroke: A Randomized,
Double-Blind, Placebo-Controlled Study of Viprinex™ (Ancrod
Injection) in Subjects Beginning Treatment within 6 Hours of the
Onset of Acute, Ischemic Stroke
PULMONARY DISEASE & CRITICAL CARE SERVICE, DEPARTMENT OF MEDICINE
Caras WE
#205032
Clagett CL
#206083
Mysliwiec V
#206086
Niven AS
#205128
T L Adjunctive Role of Mirtazapine in Mild Positional Sleep Apnea
T M A Randomized, Double-blind, Placebo-controlled, Parallel Group,
Stratified, Multi-center, 12 Week Study Comparing the Safety and
Efficacy of Fluticasone and Formoterol Combination (FlutiForm™
100/10 meg twice daily) in a Single Inhaler (SkyePharma HFA
pMDI) with the Administration of Placebo or Fluticasone (100 meg
twice daily) and Formoterol (10 meg twice daily) Alone in Adolescent
and Adult Patients with Mild to Moderate Asthma
O L Identifying Adherence Obstacles to CPAP Therapy
O L Impulse Oscillometry and Obstructive Lung Disease: Assessment of
a Clinically Significant Bronchodilator Response
NUTRITION CARE DIVISION
Cates-Gorang CC
#206008
O L
Attenuation of Exertional Muscle Damage with a Nutritional
Supplement
DEPARTMENT OF NURSING
DePew CL
#206093
Jones JM
#203030
Loan LA
#205117
Loan LA
#202066
O L Effects on Aspirated Volume, Patency, and Tracheal Mucosa using
High Intermittent Negative Pressure versus Low Continuous
Negative Pressure for Subglottic Secretion Aspiration
C L Junior Army Nurse Corps Officers' Perceptions, Experiences and
Expectations of Head Nurse Leadership
O L A Qualitative Descriptive Study that Identifies Essential
Competencies and Leadership Characteristics of Army Adult
Medical- Surgical Critical Care Head Nurses (dissertation)
O L Caring Interventions for Couples Who Have Miscarried
48
Prin. Invest.
#Protocol No.
S T Title
Loan LA
#205037
Loan LA
#204084
Loan LA
#204031
Loan LA
#201104
O L Determining the Effectiveness of a Stroke Prevention Program
O L Impact of Inpatient Physician Order Entry on Medication
Administration and Dispensing Error Rates in the Neonatal
Intensive and Intermediate Care Units
O M Military Nursing Outcomes Database: Analysis & Expansion
(MilNOD IV)
O L Newborn Infant Speech Perception
Loan LA
#202075
McNabb LA
#206108
Trego LL
#206107
O L Secondary Analysis of NICU Modified Care Environment Projects
O L Army Nurse Corps Officers' Deployment Experiences and
Reintegration
O L Menstruation During Deployment: Women's Attitudes Towards
Menstrual Suppression
Trego LL C L Military Women's Thoughts about Menstruation and Menstrual
#206002 Suppression During Deployment
ANESTHESIA STUDENTS, DEPARTMENT OF NURSING
Hannon MK C L Efficacy of Preoperative Valerian (Night Before) on Day of Surgery
#204112 Anxiety
DEPARTMENT OF OBSTETRICS/GYNECOLOGY
Burris AC
#206042
C L Resident Training in Assessment of the Sexual Assault Patient
Utilizing Simulation
Chinn MK
#205140
O L Continuous Use of the Oral Contraceptive for Menstrual Cycle
Suppression and the Effects on Bone Density; a Prospective,
Randomized, Clinical Trial
Dainty LA O G GOG 0041: Surgical Staging of Ovarian Carcinoma
#81035
Dainty LA
#81105
Dainty LA
#84033
O G GOG 0052: A Phase III Randomized Study of Cyclophosphamide
Plus Adriamycin Plus Platinol Versus Cyclophosphamide Plus
Platinol in Patients with Optimal Stage II Ovarian Adenocarcinoma
O G GOG 0072: Ovarian Tumors of Low Malignant Potential: A Study of
the Natural History and a Phase II Trial of Melphalan and
Secondary Treatment with Cisplatin in Patients with Progressive
Disease
Dainty LA
#84074
Dainty LA
#86089
Dainty LA
#87104
O G GOG 0078: Evaluation of Adjuvant VP-16, Bleomycin, and Cisplatin
(BEP) Therapy in Totally Resected Choriocarcinoma, Endodermal
Sinus Tumor, Embryonal Carcinoma and Grade 3 Immature
Teratoma of the Ovary, Pure and Mixed with Other Elements
O G GOG 0085: A Randomized Comparison of Hydroxyurea versus 5-FU
Infusion and Bolus Cisplatin as an Adjuvant to Radiation Therapy
in Patients with Stages II-B, III, and IV-A Carcinoma of the Cervix
and Negative Para-Aortic Nodes
O G GOG 0092: Treatment of Selected Patients with Stage IB
Carcinoma of the Cervix After Radical Hysterectomy and Pelvic
Lymphadenectomy: Pelvic Radiation Therapy versus No Further
Therapy
49
Prin. Invest.
#Protocol No.
S
T
Title
Dainty LA
#87028
0
G
GOG 0095: Randomized Clinical Trial for the Treatment of Women
with Selected Stage IC and II (A,B,C) and Selected IAi and IBi and
IAii and IBii Ovarian Cancer, Phase III
Dainty LA
#87091
0
G
GOG 0099: A Phase III Randomized Study of Adjunctive Radiation
Therapy in Intermediate Risk Endometrial Adenocarcinoma
Dainty LA
#93063
0
G
GOG 0123: A Randomized Comparison of Radiation Therapy &
Adjuvant Hysterectomy vs Radiation Therapy & Weekly Cisplatin &
Adjuvant Hysterectomy in Patients with Bulky Stage IB Carcinoma
of the Cervix
Deering SH
#206029
0
L
Simulation Training for Postpartum Hemorrhage
Flood SK
#206098
0
L
Serum Estradiol Levels in Patients with Polycystic Ovarian
Syndrome undergoing Ovulation Induction with Clomiphene Citrate
Han JJ
#99077
c
L
Misoprostol for the Medical Management of Non-viable First
Trimester Pregnancies
Hill DL
#204111
0
M
Glyburide Compared to Insulin in the Management of White's
Classification A2 Gestational Diabetes
Hill DL
#206099
0
L
Molecular mechanisms of progesterone mediated inhibition of LPS
and other inflammatory agent induced production of pro-
inflammatory cytokines in the fetal-maternal circuitry of the human
placenta
Howard BC
#203067
0
L
The Effects of IL-10 on the Production of Inflammatory Cytokines in
a Placental Artery Explant Model
Howard BC
#203066
0
L
The Production of Immunoregulatory Cytokines in a Placental
Artery Explant Model
Howard BC
#204088
0
M
Use of Transvaginal Cervical Length Measurements in Twin
Gestations
Lattu AL
#205005
0
L
The Distribution of Bishop Scores and Quantitative Values of Fetal
Fibronectin (fFN) in Nulliparous Patients Between 37-42 Weeks
Gestation: A Prospective Observational Study
Lattu AL
#203078
0
L
Use of Pipelle Endometrial Sampling in the Evaluation of Abnormal
First Trimester Pregnancy
Manshande MM
#205089
0
L
Pilot Study of a Novel Cord Blood Collection Technique
Napolitano PG
#203045
0
M
Randomized Controlled Trial of Endurance Exercise and
Gallbladder Disease Risk in Overweight Pregnant Women
Napolitano PG
#203001
0
B
The Effect of Magnesium on Matrix Metalloproteinase-9 Activity in
Umbilical Cord Blood at Delivery of Pregnancies Complicated by
Chorioamnionitis
Napolitano PG
#203099
0
L
Umbilical Cord Plasma Homocysteine Concentrations at Delivery in
Pregnancies Complicated by Preeclampsia
Paonessa DJ
#204108
c
L
The Effects of Cholic Acid and Deoxycholic Acid on Placental Artery
Perfusion Pressures in the Ex Vivo Placental Cotyledon Model
Zalucki CM
#205021
0
L
Correlation of Persistent Anal Sphincter Defects and Symptoms
following Repair of Anal Sphincter Lacerations due to Obstetric
Injury in Primiparous Women
50
Prin. Invest. S T Title
#Protocol No.
DEPARTMENT OF PATHOLOGY
Ager EP
#203095
T
M
Implementation of the SARS Coronavirus Real-Time PCR Primers
and Probes Assay to Detect SARS Coronavirus in Respiratory
Specimens
Ager EP
#203041
0
M
Use of a Non-FDA Approved Gene Amplification Test To Detect or
Rule-Out Vaccinia in Patients With Complications Following
Smallpox Vaccination or Possible Contact Vaccinia
Andrews JM
#205102
0
L
Absolute Lymphocytosis in Adults: A Laboratory Protocol
Champeaux AL
#205042
0
L
Incidental Anatomic and Histologic Findings in Bariatric Surgery
Specimens
DEPARTMENT OF PEDIATRICS
Cason RL
#203014
T
L
Clinical Use of Reticulocyte Hemoglobin to Detect Iron Deficiency at
the 12 Month Well Baby Visit
Davis BE
#204104
0
M
Health, Quality of Life & Activity in Cerebral Palsy
Davis BE
#204074
0
M
Survey of Chronic Pain and Its Effects on Youth With Disabilities
Ervin MK
#206049
0
L
An Observational Study to Determine the Factors Influencing Bone
Mineral Density in Post-Menarchal Adolescents with
Neuromuscular Disabilities
Fairchok MP
#205138
0
M
Evaluation of Serologic Responses to Fluzone® in Infants > 6
Months of Age Who Did or Did Not Receive Fluzone Vaccine at 2
Months of Age
Fairchok MP
#203052
c
M
Improving the Delivery of Influenza Vaccine to Young Children: A
Comparison of Two Influenza Vaccine Regimens
Fairchok MP
#205137
T
M
Safety and Immunogenicity of Fluzone® Influenza Virus Vaccine
(2005-2006 Formulation) Among Healthy Children 6 to 12 Weeks of
Age
Fairchok MP
#205034
c
M
Safety and Immunogenicity of Influenza Virus Vaccine Fluzone®
2004-2005 Among Healthy Children 2 Months vs 6 Months of Age
Fairchok MP
#205139
0
L
The Impact of Human Metapneumo virus Versus other Common
Respiratory Viruses in Infants in Fulltime Daycare
Fitzgerald KL
#206035
0
M
Military Children at Risk - Enhancing Quality of Life (mCARE)
Needs Assessment
Gries DM
#205065
0
L
Staphylococcus Aureus Intestinal Colonization Among Healthy
Infants
Harsha WT
#204097
T
A
Effect of Immunomodulatory Diet Upon 5-Fluorouracil Induced Oral
and Intestinal Mucostitis in Golden Syrian Hamsters (Mesocricetus
auratus)
Johnson ER
#206021
0
L
EKG Screening in ROTC Cadets; Is It Useful?
Kramer LC
#203119
0
L
Alternating Antipyretics: Antipyretic Efficacy Of Acetaminophen
Versus Acetaminophen Alternated With Ibuprofen In Children
Lieuw KH
#205110
0
C
AALL03N1, Understanding the Ethnic and Racial Differences in
Survival in Children with Acute Lymphoblastic Leukemia
51
Prin. Invest.
#Protocol No.
Lieuw KH
#206052
Lieuw KH
#206095
Lieuw KH
#206096
Lieuw KH
#206051
Lieuw KH
#206097
Lieuw KH
#200032
Lieuw KH
#200077
Lieuw KH
#200139
Lieuw KH
#205015
Lieuw KH
#205068
Lieuw KH
#205095
Lieuw KH
#205067
Lieuw KH
#205026
Lieuw KH
#205122
Lieuw KH
#206034
Lieuw KH
#205084
Lieuw KH
#203024
Lieuw KH
#205047
S T Title
0 C ACNS0331 A Study Evaluating Limited Target Volume Boost
Irradiation and Reduced Dose Craniospinal Radiotherapy (18.00 Gy)
and Chemotherapy in Children with Newly Diagnosed Standard
Risk Medulloblastoma: A Phase III Double Randomized Trial
0 C AEWS02B1, A Group wide Biology and Banking Study for Ewing
Sarcoma
0 C AHOD0431, A Phase III Study for the Treatment of Children and
Adolescents with Newly Diagnosed Low Risk Hodgkin Disease
O M ANBL0032 Phase III Randomized Study Of Chimeric Antibody
14.18 (Chl4.18) In High Risk Neuroblastoma Following
Myeloablative Therapy And Autologous Stem Cell Rescue
O C AREN03B2; Renal Tumors Classification, Biology, and Banking
Study
C C COG 9900, ALinC 17, Classification (C), B-Precursor Induction
Treatment (I) Protocol
O C COG 9904, ALinC 17: Treatment for Patients with Low Risk Acute
Lymphoblastic Leukemia, A Phase III Study
O C COG A5971: Randomized Phase III Study for the Treatment of
Newly Diagnosed Disseminated Lymphoblastic Lymphoma or
Localized Lymphoblastic Lymphoma, A Phase III COG Study
O C COG AALL0031, A COG Pilot Study for the Treatment of Very High
Risk Acute Lymphoblastic Leukemia in Children and Adolescents
O C COG AALL0232, High Risk B-precursor Acute Lymphoblastic
Leukemia
O C COG AALL0331, Standard Risk B-precursor Acute Lymphoblastic
Leukemia; A Phase III Group-Wide Study
O C COG AALL03B1, Classification of Acute Lymphoblastic Leukemia
C C COG AAML03P1, Treatment of Newly Diagnosed Childhood Acute
Myeloid Leukemia (AML) Using Intensive MRC-Based Therapy and
Gemtuzumab Ozogamicin (GMTZ): A COG Pilot Study
C C COG ACNS0126, A Phase II Study of Temozolomide in the
Treatment of Children with High-grade Glioma or diffuse intrinsic
Pontine Gliomas
O C COG ACNS0423: A Phase II Study of Concurrent Radiation and
Temozolomide Followed by Temozolomide and Lomustine (CCNU) in
the Treatment of Children with High Grade Glioma
O C COG AGCT0132, A Phase III Study of Reduced Therapy in the
Treatment of Children with Low and Intermediate Risk
Extracranial Germ Cell Tumors
O C COG AHOD0031, A Phase III Group-wide Study of Dose-intensive
Response-based Chemotherapy and Radiation Therapy for Children
and Adolescents with Newly Diagnosed Intermediate Risk Hodgkin
Disease
C C COG AHOD00P1, A Pilot Study of Re-Induction Chemotherapy with
Ifosfamide, and Vinorelbine (IV) in Children with
Refractory/Relapsed Hodgkin Disease
52
Prin. Invest.
#Protocol No.
S T Title
Lieuw KH
#205014
Lieuw KH
#201108
Lieuw KH
#205069
Lieuw KH
#200049
Lieuw KH
#98090
Lieuw KH
#201054
Lieuw KH
#205105
Lieuw KH
#94092
Lieuw KH
#95058
Lieuw KH
#96097
Lieuw KH
#200018
Lieuw KH
#200048
Lieuw KH
#203105
Maranich AM
#206045
Moffitt DR
#204040
Puntel RA
#204028
Puntel RA
#203046
0 C COG AHOD0321, A Phase II Study of Weekly Gemcitabine and
Vinorelbine in Children with Recurrent or Refractory Hodgkin
Disease
0 C COG ANBL00B1, Neuroblastoma Biology Studies
C C COG ANHL0121, A Phase II Study of Rituximab (IND#7028) and
Ifosfamide, Carboplatin and Etoposide (ICE) Chemotherapy in
Children with Recurrent/Refractory B-cell (CD20+) Non-Hodgkin
Lymphoma and B-cell Acute Lymphoblastic Leukemia
O C COG D9902, A COG Soft Tissue Sarcoma Diagnosis, Biology and
Banking Protocol
O C COG P9442: National Wilms Tumor Late Effects Study
C C COG P9934: Systemic Chemotherapy, Second Look Surgery and
Conformal Radiation Therapy Limited to the Posterior Fossa and
Primary Site for Children > 8 Months and < 3 Years with Non¬
metastatic Medulloblastoma - A Children's Oncology Group Phase
III Study
O C COG-LTF, A Groupwide Process for Collecting Long Term Follow
Up Data
O C POG 9351/CCG 7921: Trial of Doxorubicin, Cisplatin, and
Methotrexate With and Without Ifosfamide, With and Without
Muramyl Tripeptide Phosphatidyl Ethanolamine (MTP-PE) for
Treatment of Osteogenic Sarcoma
C C POG 9400: ALinC 16 Classification (C) Protocol
O C POG 9440: National Wilms Tumor Study - 5: Therapeutic Trial and
Biology Study
C C POG P9761: Phase II Trial of Irinotecan in Children with Refractory
Solid Tumors: A COG Study
O C POG P9851: Osteosarcoma Biology Protocol, Companion to Group-
Wide Therapeutic Studies
C C POG P9962 A Phase II Study of Intrathecal Topotecan in Patients
with Refractory Meningeal Malignancies
C L The Pontine Valentine Leucocidin Virulence Factor in Staph Aureus
Disease: A Retrospective Study Analyzing CA-MRSA Incidence and
Clinical Severity
O M National Cystic Fibrosis Foundation Patient Data Registry
O A Pediatric Intubation Training Utilizing the Ferret (mustela putorius
furo) Model
O M Telemedicine Based Ultrasound for Detecting Neonatal Heart
Disease in Babies at Remote Military or Native American Health
Care Facilities
DEPARTMENT OF PHARMACY
Booth HS C L Assessment of LDL-Cholesterol Goal Attainment Among Patients at
#206092 a Very High Risk For Secondary Cardiovascular Events in a
Pharmacist-Managed Lipid Clinic
53
Prin. Invest.
#Protocol No.
S T Title
DEPARTMENT OF PREVENTIVE MEDICINE
Hoang HV
#206056
C
L
Will Power: Is Personal Motivation Associated with Retention in the
Army?
Hughes VR
#206066
C
L
Self Identification as a Predictor of Subsequent Mental Health
Diagnosis
Moores CA
#206074
C
L
Military Rank as a Risk Factor for Type 2 Diabetes in Military
Spouses
Ross TW
#206033
C
L
Hazards to Hearing and Threshold Shifts: The Results of
Deployment to a Combat Environment
Wiesen AR
#205099
O
L
CD4+ T Cell Epitope Identification for Protective Antigen of Bacillus
Anthracis
DEPARTMENT OF PSYCHIATRY
Peterson KA
#204089
O
M
A Placebo- Controlled Trial of Prazosin vs. Paroxetine in Combat
Stress-Induced Nightmares and Sleep Disturbance
Peterson KA
#206011
O
M
Prazosin for the Treatment of Trauma Nightmares in PTSD
DEPARTMENT OF PSYCHOLOGY
Darnell JN
#206062
O
L
Military Readiness Risks: Leader Perspectives Impact on Mandatory
Addiction Referrals
Johnson PL
#205019
O
L
Theory-Guided Anticipatory Guidance
Lucenko BA
#206088
O
L
Exposure to Death and Dying and Mental Health Response in
Operation Iraqi
Reger GM
#206118
O
L
User Centered Design Feedback for the Virtual Iraq
Reger MA
#206077
O
L
Army Suicide Event Report: Data Analysis
DEPARTMENT OF RADIOLOGY
Balingit AG
#202117
O
L
Intravenous Administration of 131 I-6-B Iodomethylnorcholesterol
(NP-59) for Adrenal Evaluation and Imaging
Reece WB
#206053
O
M
NSABP B-39 / RTOG 0413 A Randomized Phase III Study of
Conventional Whole Breast Irradiation (WBI) Versus Partial Breast
Irradiation (PBI) for Women with Stage 0, I or II Breast Cancer
Reece WB
#204069
O
S
SWOG RTOG 0212, A Phase II/III Randomized Trial of Two Doses
(Phase Ill-Standard vs. High) and Two High Dose Schedules (Phase
Il-Once vs Twice Daily) for Delivering Prophylactic Cranial
Irradiation for Patients With Limited Disease Small Cell Lung
Cancer
Semerad DC
#205134
O
L
Clinical Trial and Retrospective Review to Determine the Sensitivity
and Specificity of Iminodiacetic Acid Scintigraphy for Fibrolamellar
Carcinoma
Statler JD
#205051
O
L
Carotid Stenosis: Digital Subtraction Angiography, Magnetic
Resonance Angiography, and the Evolution of Preoperative
Evaluation
Statler JD
#205024
O
L
Computed Tomography of the Abdomen Following Appendectomy
54
Prin. Invest.
#Protocol No.
S T Title
SPECIAL FORCES GROUP, FORT LEWIS
Wendt EP
#206106
0
A
1st Special Forces Group (Airborne) Combat Trauma Management
Procedures Training for Special Forces Medical Personnel
Wendt EP
#206018
0
A
1st Special Forces Group (Airborne) Instructing Combat Trauma
Management to Trainees
GENERAL SURGERY SERVICE, DEPARTMENT OF SURGERY
Arthurs ZM
#206032
0
L
Colonic Ischemia Following Abdominal Aortic Aneurysm Repair- -
Open vs. Endovascular Approaches
Arthurs ZM
#206123
0
L
Renovascular Hypertension: A Retrospective Analysis of Renal
Artery Stenting Outcomes
Arthurs ZM
#203090
0
L
The Association Of Elevated C-Reactive Protein With Presence And
Degree Of Carotid Stenosis
Azarow KS
#203107
C
M
A Multicenter, Open-Label, Randomized Study To Compare The
Safety And Efficacy Of Once Daily Levofloxacin Along With Once
Daily Metronidazole Versus Piperacillin / Tazobactam In The
Treatment Of Complicated Appendicitis, Protocol CAPSS-151
Azarow KS
#204013
C
L
Abdominal Wall Defects: Does the Intraabdominal Pressure Affect
Outcome?
Beekley AC
#204058
0
A
Advanced/Combat Trauma Management Training Using Animal
Models (Domestic Goat/Capra hircus, Pig/Sus scrofa)
Beekley AC
#205075
0
L
Operation Iraqi Freedom Combat Trauma Database from the 31st
Combat Support Hospital, Baghdad, Iraq
Brown TA
#204106
C
M
A Multicenter, Double-blind, Randomized, Phase 3 Study to
Compare the Safety and Efficacy of Intravenous Doripenem with
that of Meropenem in Complicated Intra-abdominal Infections
Brown TA
#206015
0
M
A Prospective Randomized Study Comparing Sentinel Lymph Node
(SLN) Evaluation with Standard Pathological Evaluation for the
Staging of Colon Carcinoma
Brown TA
#205074
C
M
A Randomized, Double-Blind Study of GT267-004 Versus
Vancomycin, and GT267-004 Versus Metronidazole, in Patients with
C. Difficile-Associated Diarrhea; Protocol GD3-170-301
Brown TA
#205096
C
M
ACOSOG Z4031, Use of Proteomic Analysis of Serum Samples for
Detection of Non- Small Cell Lung Cancer
Brown TA
#206101
0
M
ACOSOG Z6041: A Phase II Trial of Neoadjuvant Chemoradiation
and Local Excision for uT2uN0 Rectal Cancer
Brown TA
#205098
T
M
ACOSOG Z9031, A Phase III Randomized Study of Preoperative
Radiation Plus Surgery Versus Surgery Alone for Patients with
Retroperitoneal Sarcomas (RPS)
Brown TA
#205097
T
M
Biological Relevance of Sentinel Lymph Node (SLN)
Micrometastasis in Patients With Colon Carcinoma
Brown TA
#203077
E
A
Comparative Medical/Surgical Research and Development (Limited)
Brown TA
#206110
0
A
Comparative Medical/Surgical Research and Development (Limited)
Brown TA
#205112
0
S
RTOG 0412 / SWOG S0332, Phase III Randomized Trial of
Preoperative Chemotherapy Versus Preoperative Concurrent
Chemotherapy and Thoracic Radiotherapy Followed By Surgical
Resection and Consolidation Chemotherapy in Favorable Prognosis
Patients with Stage IIIA (N2) Non-Small Cell Lung Cancer
55
Prin. Invest.
#Protocol No.
Brown TA
#205113
Brown TA
#205114
Carter PL
#202013
Cronk DR
#204001
Cronk DR
#206040
Cuadrado DG
#206041
Cuadrado DG
#203114
Cuadrado DG
#206016
Cuadrado DG
#203034
Eckert MJ
#206047
Eckert MJ
#206115
Eckert MJ
#205080
Eggebroten WE
#204101
Hartenstine MJ
#204100
Herbert GS
#206026
Herbert GS
#206010
Herbert GS
#201020
Herbert GS
#206027
Herbert GS
#205125
Herbert GS
#205126
Herbert GS
#205063
Husain FA
#202073
S T Title
C S SWOG 9430, A Phase II Trial of Complete Surgical Resection for
Stage IV Melanoma - Surgical Resection With Biological Evaluation
And Clinical Follow-Up
C S SWOG 9431, Cytogenetic Molecular and Cellular Biology Studies in
Metastatic Melanoma Patients, Ancillary
O L Bariatric Surgery Effects on the Comorbidities of Obesity
O L Does Intestinal Fatty Acid Binding Protein Predict Strangulation in
Mechanical Small Bowel Obstruction?
O L Does SDF-1 Production by Atherosclerotic Plaques Correlate with
Severity of Carotid Artery Stenosis?
O L Breast Abscesses Following Nipple Piercing: A Case Series and
Review of the Literature
C L Chewing Gum for the Reduction of Postoperative Ileus After
Elective Open Colectomy
T L Determining the Incidence of Sonographically Detectable Wound
Seromas in the Morbidly Obese: A Pilot Study
O L Impact of Gastric Bypass with Subtotal Gastrectomy on Plasma
Ghrelin Profile
C L Bronchoscopy in the Blast Injury Patient
O A Hypoxemic Reperfusion Following Lower Torso Ischemia in sp. Sus
scrofa
O A Stem cell engraftment in the lipopolysaccharide mouse (Mus
musculus) model of acute inflammatory injury
T A Advanced Trauma Life Support (ATLS) Training Utilizing the Goat
(Capra hircus)
O L Human Blood Collection for Bench Research Initiatives
O L Determination of Telomerase Activity in Atypical Ductal
Hyperplasia of the Breast
O L Does Control of Inflammation Prior to Intervention for Carotid
Artery Disease or Lower Extremity Peripheral Arterial Disease
Affect Outcome?
O L Learning Curves for Airway Assessment and Endotracheal
Intubation - Cumulative Sum Analysis
O L Prognostic Significance of Telomerase Activity in T1 and T2 Rectal
Adenocarcinoma for Patients Undergoing Transanal Excision
O L Prospective, Randomized, Placebo- Controlled Trial of Tegaserod for
Treatment of Delayed Gastric Emptying after
Pancreaticoduodenectomy
O L Prospective, Randomized, Placebo- Controlled Trial of Tegaserod for
Treatment of Post-Operative Ileus Following Partial Colectomy
O L The Impact of Nodal Micrometastases on Survival of Women with
Breast Cancer
T M Ultrasound Imaging for Central Venous Catheter Placement in the
Intensive Care Unit: Is Real-time Really Better? A Prospective
Randomized Trial
56
Prin. Invest.
#Protocol No.
S
T
Title
Kjorstad RJ
#206043
O
L
Colorectal Complications of External Beam Radiation vs.
Brachytherapy for Prostate Cancer
Kjorstad RJ
#205127
T
L
Screening for Occult Vascular Injuries Utilizing a Portable
Ultrasound Unit
Martin MJ
#206079
O
L
The Utility and Impact of Standard Trauma Triage Criteria in the
Elderly
Mullenix PS
#203091
T
L
Prospective Evaluation Of Intraoperative Duplex Ultrasound As An
Adjunct To Technical Excellence During Carotid Endarterectomy
Perry JT
#206061
O
L
Utilization of Genetic Testing and Counseling Among Patients with
Hereditary Non-Polyposis Colorectal Cancer
Perry JT
#206038
O
L
Venous Distensibility Index as a Predictor of Radiocephalic
Arteriovenous Fistula Maturation
Sohn VY
#206116
O
L
Breast Papillomas in the Era of Stereotactic Core Biopsy
Sohn VY
#206114
O
L
Institutional Accuracy of 11- and 8- Gauge Vacuum-Assisted Core
Biopsy of Mammographic Breast Lesions
Sohn VY
#206004
O
A
The Evaluation of Telomerase Inhibition in a Colorectal Metastasis
Model Using Nude Mice (Mus musculus)
OPHTHALMOLOGY SERVICE, DEPARTMENT OF SURGERY
Ainbinder DJ
#204085
C
L
Flow Cytometry Descriptive Findings from Lacrimal Sac Biopsy
Specimens, Obtained in Standard Dacryocystorhinostomy
Boden JH
#206076
C
L
Methicillin Resistant Ascending Facial and Orbital Cellulitis in
Operation Iraqi Freedom Troop Population
Boden JH
#206124
O
L
The use of lidocaine gel prior to povidone - iodine antisepsis and its
effect on microbial survivability
Solverson DJ
#206006
O
L
Virtual Ophthalmosurgical Simulator as a Valid Training Tool
Torres MF
#204049
C
L
Long-Term Follow-up of Military Personnel Following
Photorefractive Keratectomy With Mitomycin- C
Torres MF
#205083
O
L
Ophthalmic Phentolamine Multiple Dose Clinical Trial
ORTHOPEDICS SERVICE, DEPARTMENT OF SURGERY
Antosh IJ
#206022
O
L
Accuracy of Reduction Utilizing Volar Fixation for Dorsally
Displaced Fractures of the Distal Radius
Arrington ED
#206037
O
L
A Retrospective Review of Injuries Sustained During Operation Iraq
Freedom and Operation Enduring Freedom Requiring Medical
Evacuation to a Tertiary Medical Center
Arrington ED
#201015
O
B
Biomechanics of Various Coracoclavicular Ligament Reconstruction
Techniques
Arrington ED
#204051
O
L
Efficacy of Post-operative Hip Spica Wrap Dressing after Primary
Hip Arthroplasty in Preventing Post-operative Wound
Complications and Blood Transfusions
Arrington ED
#203036
O
L
Intramedullary Fixation of Displaced Acute Middle One-Third
Clavicle Fractures
Arrington ED
#206085
O
L
Pectoralis Major Repairs in Active Duty Soldiers
Arrington ED
#206036
O
L
Return to Full Duty after Anterior Cruciate Ligament
Reconstruction in the Military Population
57
Prin. Invest.
#Protocol No.
S
T
Title
Arrington ED
#200065
c
M
Study of the Treatment of Articular Repair (STAR): A Prospective,
Longitudinal Within Patient Evaluation of the Effectiveness
(Durability) of Carticel (autologous cultured chondrocytes)
Compared to Non-Carticel Surgical Treatment for Articular
Cartilage Defects of the Knee
Arrington ED
#200125
O
L
Subacromial Injection of Corticosteroids versus Ketoralac for
Treatment of Shoulder Impingement Syndrome
Benfanti PL
#205300
O
M
Stryker Biotech- OP-1 Bone Morphogenetic Protein, BMP-7 (HUD)
DeVine JG
#205053
O
M
A Prospective, Randomized Clinical Investigation of the Cervitech,
Inc. Porous Coated Motion Artificial Disc for Stabilization of the
Cervical Spine at One Level between C3-C4 and C7-T1
DeVine JG
#206120
O
M
A Single Blind, Multi- Center, Randomized, Prospective Clinical
Study Comparing Optecure™ Autograft Extender to Autograft Only
in Fusion of the Lumbar Spine
DeVine JG
#206081
O
L
Magnetic resonance imaging evaluation of adjacent segments after
lumbar disc arthroplasty using the SB Charite implant
Devine JG
#206082
O
L
Magnetic Resonance Imaging Evaluation of Adjacent Segments
After Cervical Disc Arthroplasty Using the PCM Implant
Driver VR
#205054
c
M
A Phase 2, Double-Blind, Randomized, Placebo- Controlled, Dose-
Ranging Study to Evaluate the Efficacy and Safety of Three Doses of
TAK-128 in Subjects with Mild to Moderate Diabetic Peripheral
Neuropathy
Driver VR
#204098
T
L
Cost of Treating Diabetic Foot Ulcers - At Madigan Army Medical
Center
Ghidella SD
#205013
O
M
A Double-blind, Randomized, Placebo-controlled Phase 2b Study to
Establish the Effective Dose Range and to Evaluate the Safety of
Chrysalin in Adult Subjects with a Fractured Distal Radius
Ghidella SD
#206009
O
L
A Randomized Study of Volar Fixed-Angle Plate Fixation Versus
Closed Management for Fractures of the Distal Radius
Ghidella SD
#205079
O
A
Microsurgery Training Utilizing The Rat (rattus norvegieus) as a
Teaching Model
Herzog JP
#201112
c
L
Post-operative Shoulder Pain: A Prospective Randomized Trial
Comparing the Pain Infusion Pump to the Pre-induction
Interscalene Block
Schweinberger MH
#202091
T
L
A Prospective, Randomized, Stratified, Parallel Group, Comparison
Study of the Healing Rate of Chronic Neuropathic Ulcers Treated
with Hyalofill versus Regranex
OTOLARYNGOLOGY SERVICE, DEPARTMENT OF SURGERY
Baumgartner BJ
#204009
c
L
Evaluation of Dizziness / Vertigo by MRI/MRA: A Clinical Outcomes
Study
Crawford JV
#205052
O
M
MET™ Fully Implantable Ossicular Stimulator Clinical Trial
Protocol
Crawford JV
#204042
T
M
Rapid Employment of Acetylcysteine Treatment for Otologic
Recovery (REACTOR), A Prospective, Multicenter, Randomized,
Double-blind, Parallel, Placebo-controlled Study Assessing the
Efficacy of the Nutritional Supplement N- Acetylcysteine Treatment
of Acute Acoustic Trauma
58
Prin. Invest.
#Protocol No.
S
T
Title
Demars SM
#206058
c
L
Effect of Smoking on Rate of Post-tonsillectomy Hemorrhage
Demars SM
#206044
c
L
Review of Postoperative Complications after BAHA Implantation at
Madigan AMC and Virginia Mason MC
Grafenberg MR
#205050
O
L
Celecoxib Versus Oxycodone in Uvulopalatopharyngoplasty Surgery:
A Comparison of Post-Operative Risks and Benefits
Grafenberg MR
#205120
O
L
Complications and Audiologic/Tympanometric Findings in Children
with Cleft Lip/Palate and Cleft Palate
Poss JM
#206125
O
L
Base of Tongue Reduction for Persistent Obstructive Sleep Apnea
Using the Coblator II System: A Pilot Study
Poss JM
#206020
O
L
Clinical Survey of Community Physicians: Post-Tympanostomy
Tube Placement and Swimming Precautions/Treatment Otitis Media
with Effusion
Sorensen DM
#203016
E
A
Pediatric Bronchoesophagology Laboratory Using Swine (Sus scrofa)
Sorensen DM
#206030
O
A
Pediatric Bronchoesophagology Laboratory using Swine (Sus scrofa)
Sorensen DM
#204070
O
L
Perioperative Immunonutrition in Head and Neck Cancer
Spear SA
#206057
O
L
Review of Thyroid Cancer Treatment Outcomes at a Major Medical
Center from 1996-2000
Thomas RF
#205009
O
L
Inferior Turbinate Reduction Comparing Turbinate Microdebrider,
Coblation and Bipolar Cautery
UROLOGY SERVICE, DEPARTMENT OF SURGERY
Baker KC
#205129
T
M
A Multi-Center, Open-Label Evaluation of the Safety of Silodosin in
the Treatment of the Signs and Symptoms of Benign Prostatic
Hyperplasia, Protocol #SI040011
Baker KC
#205092
O
M
A Multi-center, Randomized Clinical Investigation of TrelstarTM
Versus Continued Therapy in Patients Receiving Lupron or Zoladex
for Advanced Prostate Cancer
Baker KC
#205072
c
M
A Multi-Center, Randomized, Double-Blind, Placebo Controlled,
Parallel Evaluation of the Efficacy and Safety of Silodosin in the
Treatment of the Signs and Symptoms of Benign Prostatic
Hyperplasia, Protocol # SI04009
Baker KC
#203035
O
M
A Multi-Institutional Pilot Study to Evaluate Molecular Markers in
Urine and Serum in the Early Detection of Prostate Cancer
Baker KC
#201113
O
M
A Phase III, Extension Study to Evaluate the Safety of 10 mg
Atrasentan in Men with Hormone-Refractory Prostate Cancer (MOO-
258)
Baker KC
#201107
O
M
A Phase III, Randomized, Double-Blind, Placebo- Controlled Study of
the Safety and Efficacy of 10 mg Atrasentan in Men with Metastatic,
Hormone-Refractory Prostate Cancer (MOO-211)
Baker KC
#201121
O
M
A Phase III, Randomized, Double-Blind, Placebo-Controlled Study of
the Safety and Efficacy of 10 mg Atrasentan in Men with Non-
Metastatic, Hormone-Refractory Prostate Cancer (MOO-244)
Baker KC
#204005
O
M
A Phase III, Randomized, Double-Blind, Placebo- Controlled Trial
Evaluating the Ability of Risedronate to Prevent Skeletal Related
Events in Patients with Metastatic Prostate Cancer Commencing
Hormonal Therapy, Protocol #GU02-41
59
Prin. Invest.
#Protocol No.
Baker KC
#204122
Baker KC
#206100
Baker KC
#206072
Baker KC
#205006
Baker KC
#204091
Baker KC
#204025
Baker KC
#205119
Baker KC
#205017
Baker KC
#204121
Baker KC
#206039
Baker KC
#204120
Baker KC
#205040
Baker KC
#204079
DeCastro BJ
#202065
DeCastro BJ
#205136
Nelson DM
#205076
O'Reilly KJ
#203053
S T Title
CM A Randomized, Double Blind, Placebo Controlled, Four Arm
(Placebo, Tolterodine ER, Tamsulosin, and Tolterodine ER plus
Tamsulosin) Study to Evaluate the Clinical Efficacy and Safety of
Tolterodine ER 4 mg in Men who have Frequency and Urgency, with
or without Urinary Urge Incontinence, with or without Bladder
Outlet Obstruction, Protocol Number A6121120
O M A Randomized, Double-Blind, Multicenter Study of Denosumab
Compared with Zoledronic Acid (Zometa®) in the Treatment of Bone
Metastases in Men with Hormone-Refractory Prostate Cancer
(20050103)
O M A Randomized, Double-Blind, Placebo- Controlled, Multi-Center
Phase 3 Study of Denosumab on Prolonging Bone Metastasis-Free
Survival in Men with Hormone-Refractory Prostate Cancer
O M A Randomized, Double-Blind, Placebo- Controlled, Multicenter
Efficacy and Safety Study of Toremifene Citrate for the Prevention
of Bone Fractures in Men with Prostate Cancer on Androgen
Deprivation Therapy (Protocol #G300203)
O M A Randomized, Double-Blind, Placebo- Controlled Study to Evaluate
AMG 162 in the Treatment of Bone Loss in Subjects Undergoing
Androgen-Deprivation Therapy for Non-Metastatic Prostate Cancer
C M An Evaluation of Semen Characteristics after 40 Weeks Daily
Dosing with 20 mg Tadalafil
O L Expression of CXCR4 in Archived Prostate Cancer Specimens and
its Association with Patient Demographics, Pathologic Results, and
Outcomes
O A Madigan Army Medical Center Advanced Laparoscopic Training
Using the Pig (Sus scrofa)
T L Prevalence of PCR Detectable Human Papillomavirus (HPV) in
Sexually Active Males - A Comparison of Specimen Collection
Methods and Genitourinary Sites
O M SEER Rapid Response Surveillance Study #5, Prostate Cancer
Therapy Selection (PCATS) Study
O L The Effect of Flexible Cystoscopy on the Serum PSA Values
O L The Epidemiology of Nephrolithiasis in Soldiers Returning From
Operation Iraqi Freedom
O M Uniformed Services University National Prostate Cancer Database
for the Center for Prostate Disease Research (CPDR) with Patterns
of Care, Outcomes, and Prognostic Analyses, Protocol Number
GT90CM
O M Oral Ketoconazole For Prevention Of Postoperative Penile Erection,
A Prospective, Randomized, Double Blind Trial
O L The Incidence of Infection and Stent Colonization in Patients With
and Without Strings
O L Madigan Army Medical Center's Current Clinical Practice and
Experience With Osteopenia And Fractures In Men Treated With
Androgen Deprivation Therapy
CM A Clinical Trial Evaluating the Safety and Efficacy of ABX-EGF in
Patients with Hormone Resistant Prostate Cancer Elevated PSA
With or Without Metastasis, Protocol Number ABX-0310
60
Prin. Invest.
#Protocol No.
O’Reilly KJ
#205033
O’Reilly KJ
#206024
O’Reilly KJ
#204116
Peterson AC
#205073
Peterson AC
#205086
Peterson AC
#205116
Peterson AC
#205027
Peterson AC
#203042
Peterson AC
#205135
Peterson AC
#206031
Peterson AC
#206117
Peterson AC
#202122
Peterson AC
#204078
S T Title
CM A Phase 2, 8-Week, Multi-Center, Randomized, Double-Blind,
Placebo- Controlled, Parallel Group Study Evaluating the Efficacy,
Tolerability and Safety of [S,S]-Reboxetine (PNU-165442G) for
Stress Urinary Incontinence in Women, Protocol A6061023
T M A Twelve-Week Randomized, Double-Blind, Placebo- Controlled,
Parallel Group, Forced Titration, Proof of Concept Study to Assess
the Efficacy, Safety and Tolerability as well as the Pharmacokinetic
Profile of 60 mg and 120 mg of GW679769 (GW679769)
administered once daily vs. Placebo in Women with Overactive
Bladder
C M Phase 2, Multi-Center, Randomized, Double-blind, Placebo-
Controlled, 3 Arm, 12-Month Study to Evaluate the Effects of GPI
1485 on Erectile Function in Patients Undergoing Bilateral Nerve-
Sparing Radical Retropubic Prostatectomy for Prostatic Carcinoma,
Protocol Number 0501-0202
O M A Phase 2, Randomized, Multicenter, Placebo- Controlled, Double-
Blind Dose-Ranging Clinical Trial to Study the Efficacy and Safety
of 5, 15, or 25 mg/day of CyPat™ (Cyproterone Acetate) for the
Treatment of Hot Flashes following Surgical or Medical Castration
of Prostate Cancer Patients, Protocol #DR-PCA-201
CM A Randomized, Double Blind, Placebo and Active-Controlled Efficacy
and Safety Study of SSR240600C, in Patients with Overactive
Bladder or Urge Urinary Incontinence, Protocol # ACT 5190
T M A Randomized, Double-Blind, Parallel-Design, Placebo Controlled
Study to Evaluate the Effects of 5 mg Tadalafil (IC351, LY450190)
and 50 mg Sildenafil Administered Once Daily for 6 Months on
Visual Function in Healthy Subjects or Subjects with Mild Erectile
Dysfunction, Protocol H6D-MC-LVGO
O M A Randomized, Double-Blind, Placebo- Controlled, Multicenter
Efficacy and Safety Study of Toremifene Citrate for the Prevention
of Prostate Cancer in Men with High Grade Prostatic Intraepithelial
Neoplasia (PIN)
O M A Randomized, Double-Blind, Placebo- Controlled, Parallel Group
Study of the Efficacy and Safety of Dutasteride 0.5 mg Administered
Orally Once Daily for Four Years to Reduce the Risk of Biopsy-
Detectable Prostate Cancer, Protocol Number ARI40006
O L Acute Urinary Retention and the Role of Fill and Pull Voiding Trials
O L Adult Circumcision: Template vs Standard Sleeve Technique
O L Comparison of Non-Contrast Abdominal Computed Tomography
(CT) to Contrast CT, Intravenous Pyelography (IVP) and Nuclear
Renal Scan for Determination of Renal Function: A Retrospective
Review
O L Followup of Testicular Microlithiasis in an Asymptomatic
Population
O M Long-Term Open-Label Extension Trial for Subjects Completing the
Phase 3 Trial of Fesoterodine (SP584) for the Treatment of
Overactive Bladder Syndrome
61
Prin. Invest.
#Protocol No.
S
T
Title
Peterson AC
#206102
O
M
Phase II, multicentre, randomised, double-blind, placebo-controlled,
pilot study to determine proof of efficacy, safety, tolerability and
pharmacokinetics of intravesical PSD597 in the symptomatic
management of interstitial cystitis/painful bladder syndrome
(I C/PBS)
Peterson AC
#204032
0
M
Prospective, Observational Registry and Patient Survey of the
Management of Men with Symptomatic Benign Prostatic
Hyperplasia (BPH): BPH Registry and Patient Survey Protocol
#L8890
Peterson AC
#204086
0
M
Prospective, Open-Label, Non-Comparative, Multi-Center Study to
Evaluate the Efficacy and Safety of Ciprofloxacin Extended-Release
(Cipro-XR) 1000 mg Tablets Given Once Daily for 7 to 14 Days in the
Treatment of Patients 18 Years or Older with Complicated Urinary
Tract Infections Caused by Pseudomonas Aeruginosa and Other
Common Uropathogens
Peterson AC
#203081
0
M
Study of the Safety and Effectiveness of the Mentor Two-Piece
Inflatable Penile Prosthesis, Protocol Number U108-802-4
Pugliese JM
#205088
0
L
The Value of Resistive Index: A Longitudinal Study of Confounding
Variables and Their Impact - A Pilot Study
VASCULAR SURGERY, DEPARTMENT OF SURGERY
Andersen CA
#206012
0
M
A Comparative Prospective, Randomized, Double-Masked, Parallel
Group, Sham- Controlled Trial of MIST Therapy for the Reduction of
Pain in Chronic Lower Extremity Ulcers
Andersen CA
#203079
c
M
A Double-Blind, Randomized, Parallel Group, Placebo- Controlled
Study to Evaluate the Safety and Efficacy of NM-702 in Subjects
with Intermittent Claudication, Protocol Number NCI-IC-0201
Andersen CA
#206094
0
M
A Multi-Center, Double-Blind, Randomized, Parallel, Vehicle-and
Standard Care-Controlled, Dose-Ranging Study Assessing the
Safety and Efficacy of MRE0094 Gel When Applied Topically for 90
Days to Subjects with Diabetic, Neuropathic, Foot Ulcers
Andersen CA
#205111
T
M
A Phase 3, Randomized, Double-Blind, Multinational Trial of
Intravenous Telavancin Versus Vancomycin for Treatment of
Complicated Gram Positive Skin and Skin Structure Infections with
a Focus on Patients with Infections Due to Methicillin-resistant
Staphylococcus aureus 0018
Andersen CA
#200088
C
L
A Prospective, Randomized Study Comparing the Outcome of
Carotid Endarterectomy Using New Generation Dacron or
Expanded Polytetrafluoroethylene (e-PTFE) Carotid Patching
Andersen CA
#202086
O
M
A Randomized, Controlled Multicenter Trial of Vacuum Assisted
Closure Therapy™ in the Treatment and Blinded Evaluation of
Diabetic Foot Ulcers (Protocol VAC2001-08)
Andersen CA
#202115
c
M
A Randomized, Controlled Multicenter Trial of Vacuum Assisted
Closure Therapy™ in the Treatment and Blinded Evaluation of
Amputation Wounds of the Diabetic Foot, Protocol No. VAC2001-07
Andersen CA
#203055
0
M
A Randomized, Controlled, Multicenter Trial of Vacuum Assisted
Closure Therapy™ in the Treatment and Blinded Evaluation of
Pressure Ulcers, Protocol Number VAC2001-01
Andersen CA
#205010
0
M
Linezolid In The Treatment Of Subjects With Complicated Skin And
Soft Tissue Infections Proven To Be Due To Methicillin-Resistant
Staphylococcus Aureus
62
Prin. Invest.
#Protocol No.
S
T
Title
Andersen CA
#206071
O
M
Phase 3, Multicenter, Multi-National, Randomized, Double-Blind,
Placebo Controlled Study to Evaluate the Efficacy and Safety of
Alfimeprase in Subjects with Acute Peripheral Artery Occlusion
(NAPA- 3)
Andersen CA
#205091
0
L
The Prevalence and Progression of Carotid Artery Stenosis in
Patients Undergoing Radiation for Head and Neck Cancer
Andersen CA
#203017
c
L
The Prevalence of Three Major Stroke Risk Factors in an Enrolled
Medicare Population
Roukis TS
#206127
0
M
A phase 2B long-term, randomized, open-label, safety and
tolerability trial comparing [S,S]-Reboxetine (PNU-165442G) with
routine care in patients with chronic painful diabetic peripheral
neuropathy (DPN) Study Number A6061031
Roukis TS
#206111
0
M
Pivotal Study to Evaluate the Efficacy and Safety of Dermal - Living
Skin Replacement (Dermal - LSR) in the Treatment of Chronic
Diabetic Foot Ulcers
Starnes BW
#206070
0
M
A Two-Part, Multicenter, Randomized, Double-Blind, Placebo-
Controlled, Study to Evaluate the Effect of Simvastatin, Losartan,
and Pioglitazone on Cardiovascular Disease Biomarkers in Lower
Extremity Atherosclerotic Plaque Excised from Patients with
Peripheral Arterial Disease
WEED ARMY COMMUNITY HOSPITAL
Wheeler GA CM A Phase 2 Study to Evaluate the Reactivity and Tolerability of
#205049 Intradermally Administered Doses of Coccidioidin in Human
Subjects in a Target Population
63
Detail Summary Sheets
Department of Anesthesia & Operative
Services
64
Detail Summary Sheet
Date: 30 Sep 06 Number: 206121
Status: Ongoing
Title: Comparison of Direct Versus Indirect Laryngeal Views using the Video Laryngoscope
During Standard Intubation Procedures
Principal Investigator: LTC Joseph P. Miller, MC
Department: Anesthesia & Operative Services
Facility: MAMC
Associate Investigator(s): None.
Start - Completion: Funding:
8/30/2006 - Aug 2006 DCI
Periodic Review:
N/A
Study Objective: The objectives of this study are to determine whether or not the indirect
laryngeal view offered by the video laryngoscope is superior to view seen by direct laryngoscopy,
the video laryngoscope offers improved anatomical views to the student during intubation training
and the video laryngoscope offers improved means of providing external laryngeal manipulations
to facilitate intubation.
Technical Approach: All patients intubated with the video laryngoscope will be entered into this
study. The data collection sheet will be completed at the conclusion of intubation by the
practitioner. No additional testing, or any medical interventions or practice outside the normal
operating procedure will be employed. The only difference in patient care with participants in this
study versus the currently employed airway management with the video laryngoscope, will be that
the intubator will complete a questionnaire at the conclusion of the intubation process. No
identifiers of the patient or practitioner will be on the questionnaire.
Progress: This minimal risk protocol received initial approval by the Expedited Review
Committee, effective 30 August 2006.
65
Detail Summary Sheet
Date: 30 Sep 06 Number: 204010
Status: Completed
Title: Evaluation of the Combat Medic Skills Validation Test
Principal Investigator: LTC Joseph P. Miller, MC
Department: Anesthesia & Operative Services
Facility: MAMC
Associate Investigator(s): COL (Ret) Eileen A. Hemman, PhD;
COL H. Quigg Davis, USA
COL David Gillingham, MC;
Start - Completion: Funding: Periodic Review:
1/13/2004 - Jul 2005 Triservice Nursing Research Program via The 10/14/2005
Geneva Foundation
Study Objective: (1) Operationalize, standardize, and centralize the combat medics' validation
testing as outlined in the TC (Training Circular) 8-800 using the collaboration of the joint medical
training center and the simulation center. (2) Evaluate the psychometric properties of the SACMS-
VT. (3) Test a random sample of battlefield medics (91W) to assess their combat medical readiness
skills using the SACMS-VT.
Technical Approach: This study will employ a descriptive, prospective design using various
instrument-testing techniques in which the reliability and validity of the SACMS-VT will be
tested. Once the initial reliability and validity is established, a representative, random sample of
units on Ft. Lewis with 100 91Ws that are scheduled for deployment within the next 1-2 years will
be recruited to take the SACMS-VT. The specific aim of this study is to evaluate the psychometric
properties of the SACMS-VT.
Progress: 49 subjects were enrolled in this study. Validity - Performance skills with a CVI < .75
were needle chest decompression, combitube® insertion, and AED (automatic external
defibrillator). The skill of splinting was recommended for addition to the SACMS-VT. Reliability -
There was high intra and inter-rater agreement on performance steps and skills with the
exception of Bleeding/Shock Management, spinal immobilization (supine), and extraction. The
average medics’ score on the SACMS-VT was 68%. Subjects tested better on the medical skills
than the trauma skills. When retested, there was significant improvement ( t = 3.268, d/= 7, p <
.014, two tailed) in test results. CONCLUSIONS/RECOMMENDATIONS: The results support the
validity and reliability of the SACMS-VT as an instrument to determine beginning level combat
medic competency. The skills with lower validity were related to the raters’ perception of medics’
ability and may change when test score are improved. High reliability may be related to the
expertise of the raters in this study and may change when raters of varying skill levels are used. It
is highly recommended that the critical item passing criteria be used for training only and that the
critical item designation be used for training only. For testing purposes, critical items should be if
the medic increases a casualty’s injuries during treatment or causes death through inaction or
wrong action.
IMPLICATIONS: More research is needed to determine the combat medical readiness of 91Ws
Army wide, as this subject population was characteristically novice medics with little experience.
66
Detail Summary Sheets
Department of Clinical Investigation
67
Detail Summary Sheet
Date: 30 Sep 06 Number: 203122 Status: Expired
Title: Establishment of a Limb Regeneration Program Using Notophthalmus viridescens (newt)
as the Model Organism and the Creation of a Transgenic N. viridescens Strain
Principal Investigator: Jeff M. Bullock, M.S.
Department: Clinical Investigation Facility: MAMC
Associate Investigator(s): CPT Jason A. Grassbaugh, MC
Start - Completion: Funding: Periodic Review:
9/10/2003 - Sep 2006 DCI 9/13/2006
Study Objective: Establish a limb regneration research program using Notophthalmus
viridenscens as a model organism. Create the first transgenic newt, expressing a LacZ or GFP
marker protein.
Technical Approach: Limbs or blastemas are amputated with sharp iridectomy scissors (or
suitable analog) and the epidermis is generally trimmed back to facilitate regeneration. Limb
regeneration results in a fully formed (albeit small) limb within 4-6 weeks. At this point, animals
will be returned to a recovery population tank until the regenerated limb is full size (another 1-2
months), at which time they are returned to the general population tanks. Newts are maintained
in dechlorinated tap water at 20-26C (or a salted variant) and fed live Tubifex worms (or some
variant) biweekly. Animals to be culled (after 3 amputations, aged or infirm) will be anesthetized
and killed by decapitation. Remains of non-transgenic and transgenic animals will be discarded in
accordance with hospital policy. Hormonal stimulation for the purpose of egg prodcution will
consist of 880-100 IU of human chorionic gonadotropin administered with a 21 gauge needle by IP
injection every other day into the abdomen of an adult female until the female deposits eggs. All
work will be done while the animal is anesthetized in a solution of 0.1% w/v Tricaine (3-
aminobenzoic acid ethylester methanesulfonate salt; Sigma MS222), and the animals are allowed
to recover in a solution of 0.1% W/V sulphamerazine for 24 hours before being returned to a
recovery tank. Both of thse solutions are made using dechlorinated tap water.
Progress: This protocol expired on 9-14-06 and I am in the process of analyzing several blastemas
from upper arm and wrist amputation sites for the presence of N-cadherin by western blot analysis
and immunohistochemistry of frozen sections. Upon completion of my analysis I will submit a
report of my results. If the results look encouraging I plan to write a companion protocol to further
investigate the role N-cadherin may play in tissue regeneration.
An additional goal of this protocol was to creat a transgenic newt. I have had limited success in
this. However it was recently reported that a group out of Germany has produced a transgenic
newt and the progeny from this animal are now available for purchase; thus negating the need for
additional work toward this goal.
68
Detail Summary Sheet
Date: 30 Sep 06 Number: 206122
Status: Ongoing
Title: Profiling of Proteins Extracted from Tissue Taken from Regenerating and Intact
Notophthalmus viridescens Limbs Using SELDI
Principal Investigator: Jeff M. Bullock, M.S.
Department: Clinical Investigation
Facility: MAMC
Associate Investigator(s): LTC Matthew J. Martin, MC
Start - Completion: Funding:
9/13/2006 - Sep 2009 DCI
Periodic Review:
N/A
Study Objective: Our primary objective is to produce a series of protein profiles from
regenerating and non-regenerating limb tissue. Protein profiles for each sample will be compared.
Differences in the profiles will be suggestive for which proteins may be involved in tissue
regeneration. Candidate proteins will be targeted for further research.
Technical Approach: Experimental arms will consist of the following: 1) Amputation followed by
enervation at various time points 5, 15, and 30 minutes and 1, 6, and 20-24 hours and 2, 3, 4, 5,
and 6 days. 2) Enervation only. 3) Neural transection followed immediately by amputation,
followed by blastectomy. Blastectomies will be performed when the blastemas reach the early to
mid-late bud stage, but before the pallet stage. 4) Amputation followed by blastectomy.
Blastectomies will be performed when the blastemas reach the early to mid-late bud stage, but
before the pallet stage. 5) Normal non-regenerating tissue taken from amputated limbs at time of
amputation. For all operations animals will be anesthetized by soaking in a cold (4-10 CO)
neutralized solution (pH 7.2 - 7.4) of 0.1% w/v Ethyl 3-aminobenzoate, methanesulfonic acid salt
(MS222). Forelimbs will be amputated at the mid humerus or mid radius; ulna region and
protruding bones trimmed using iridectomy scissors or a suitable analog. Amputation of the first
forelimb will be followed immediately by the amputation of the opposite forelimb. Amputated
limbs to be saved will immediately be put into cryogenic tubes and snap frozen in liquid nitrogen.
Amputees while still anesthetized will be given 100 1 of Buprenex by IP injection at a dose of
(0.01-0.03 mg/kg) diluted to a concentration of 3 X 10-4 mg/ml with a lactate ringer solution
adjusted to a mOsmol/L of 225 +/- 5 using a 5/8 inch 26 gauge needle. Following the Buprenex
injection animals are placed on an ice pack covered with a paper cloth for 15-30 minutes before
allowing them to warm and placed back into an aquarium. Nerves 3, 4, and 5 of the brachial
plexus are the main nervous supply in the newt forelimb. In animals to be enervated these nerves
will be removed by excision. Using the tip of a 5/8 inch 26 gauge needle an incision will be made
on the ventral side of the forelimb that runs along the entire length of the limbs' proximal distal
axis. The epidermis and surrounding muscle are pulled aside to expose the nerves and the
rounded bore of the needle is inserted beneath the nerve bundles and pulled along the length of
the nerve to free it from any connective tissue. Once the nerve has been exposed and freed it is
excised using iridectomy scissors or a suitable analog. Excised nerves to be saved are immediately
put into cryogenic tubes and snap frozen in liquid nitrogen. In some cases nerves 3, 4, and 5 will
not be removed, but will instead be transected at the brachial plexus. A small incision at the
brachial plexus will be made with the tip of a 5/8 inch 26 gauge needle and the nerves severed with
iridectomy scissors or a suitable analog. Animals whose nerves were removed or transected while
still anesthetized will be given 100 1 of Buprenex by IP injection at a dose of (0.01-0.03 mg/kg)
diluted to a concentration of 3 X 10-4 mg/ml with a lactate ringer solution adjusted to a mOsmol/L
of 225 +/- 5 using a 5/8 inch 26 gauge needle. Following the Buprenex injection animals are placed
on an ice pack covered with a paper cloth for 15-30 minutes before allowing them to warm and
placed back into an aquarium. If necessary, as determined by the staff veterinarian, a second and
third dose of Buprenex will be give at 20-25 hours post-op, and at 46-48 hours post-op. If possible
these injections will be given without anesthesia. In all cases (amputations, enervation, and nerve
69
transections) if Buprenex fails to provide adequate pain relief (as determined by the staff
veterinarian) we plan to try other post-op analgesics. Possible choices include: Butorphanol at 0.2-
0.4 mg/kg by IP injection, 2% Lidocaine or Bupivacaine administered topically 3-6 hours post-op
then as necessary for 24-48 hours. All post-op analgesic care decisions/changes will be at the
discretion of the staff veterinarian. Blastemas are removed by transecting the blastemas at the
amputation plane using iridectomy scissors or a suitable analog. Once the blastemas have been
removed they are immediately put into cryogenic tubes and snap frozen in liquid nitrogen.
Following blastema removal animals are placed on an ice pack covered with a paper cloth for 15-30
minutes before allowing them to warm and placed back into an aquarium. No post-op analgesics
will be given after removal of blastemas. Depending on the experimental arm an animal is placed
in it may under go multiple surgical procedures. However, once an animal has been used in one
experimental arm it will not be used in a different experimental arm or reused in the same
experimental arm. Animals that have reached the end point of an experimental arm will be
euthanized as described below. Animals to be euthanized will be placed in a 0.1 to 1.0 % w/v
buffered solution (pH 7. 2-7. 6) of MS222 for 15-30 minutes until completely sedated. Dose and
length of time of MS222 exposure will be at the discretion of the staff veterinarian. Following
sedation animals will be decapitated using iridectomy scissors or a suitable analog. All tissues
including euthanized animals will be place in the hospital trash for disposal. Tissue to be saved
will be snap frozen immediately upon removal. Proteins will be extracted from frozen tissue by
sonication and maceration in a buffered lysis solution containing protease inhibitors. Cellular
debris will be removed by centrifugation and protein concentration determined by colorimetric
spectroscopy. Protein profiles will be done using SELDI. Protein profiles from regenerating
blastema and non-regenerating limb tissue along with nerve tissue from regenerating and non¬
regenerating limbs will be compared. Differences in the profiles will be suggestive for which
proteins may be involved in tissue regeneration. Candidate proteins will be targeted for further
research.
Progress: This protocol received initial approval during a convened meeting of the IACUC on 13
September 2006, work will begin in FY 07.
70
Detail Summary Sheet
Date: 30 Sep 06 Number: 205031 Status: Ongoing
Title: Proteomic Analysis of Longitudinally-Collected Maternal Plasma Samples: Establishing
the 'Pregnancy Proteome'
Principal Investigator: CPT Michael J. Hartenstine, MS
Department: Clinical Investigation Facility: MAMC
Associate Investigator(s): CPT Patrick M. McNutt, MS; CPT Jeremy P. Celver, MS; LTC
Peter G. Napolitano, MC; COL Jerome B. Myers, MC; CPT Daniel G. Cuadrado, MC; MAJ
Jennifer L. Gotkin, MC; Danielle L. Ippolito, PhD; CPT Garth S. Herbert, MC; Heidi M.
Cederholm, B.S.; Aspen M. Bergmann, B.S.
Start - Completion: Funding: Periodic Review:
3/23/2005 - May 2006 DCI 1/24/2006
Study Objective: To determine the baseline proteome for a normal pregnancy and assess the
changes in protein among maternal plasma samples.
Technical Approach: Investigators propose to collect samples at the first OB/GYN physician
visit ( NLT 12 weeks), during the second trimester analyte screen (~16-22weeks), early third
trimester (26-28weeks), late third trimester (~36-38 weeks), upon admission for labor and at 6-10*
weeks post-partum, as well as cord blood collected at delivery. Plasma will be longitudinally
collected from 300 pregnant women to conduct a pilot analysis of 10 representative patients with
uncomplicated pregnancies at 3 time points. The preliminary results will be used for an initial
publication and to pursue more substantive funding for a detailed analysis. The samples will be
available for collaboration with other researchers under the auspices of the IRB, and under the
direction of the research operations service component of DCI.
Progress: This protocol remains open to enrollment with 121 patients enrolled at MAMC.
Significant improvement was achieved with patient enrollment during FY06. Crude samples of
seven women have been profiled, which yielded the beginnings of a proteomic fingerprint of
pregnancy. In addition to profiling samples from uncomplicated pregnancies, several miscarriage
samples have been profiled and two specific proteins have been observed to be elevated in
miscarriage samples. Collection of clinical data has begun on the patient population to better
characterize the samples in the tissue bank.
71
Detail Summary Sheet
Date: 30 Sep 06 Number: 205044
Status: Ongoing
Title: A Prospective Study of Pseudocholinesterase Activity
Chronic Pain, Pelvic Pain and Hernias
in Patients with Fibromyalgia,
Principal Investigator: CPT Patrick M. McNutt, MS
Department: Clinical Investigation
Facility: MAMC
Associate Investigator(s): CPT Daniel G. Cuadrado, MC; CPT Kathleen M. Goings, MC; CPT
Jeremy P. Celver, MS; MAJ Brian T. McKinley, MC; CPT Kyle C. Harner, MC; CPT Christopher
S. Murphy, MC
Start - Completion: Funding:
3/17/2005 - Nov 2006 DCI
Periodic Review:
2/22/2006
Study Objective: To determine if there is a correlation between levels of serum cholinesterase
and acute and chronic pain.
Technical Approach: Five separate groups will be analyzed for this protocol. Group 1, hernia
surgery, patients identified with an inguinal hernia who are scheduled for surgery with the
Department of General Surgery will be enrolled following detailed pre-operative history and
physical examination and standard pre-operative laboratory evaluation. Those enrolled in the
study will fill out a questionnaire at the time of this appointment and be consented by a member of
the study staff or resident. During their routine pre-operative blood draw an additional 3cc purple
top tube will be collected and sent to DCI. There the specimen will be centrifuged and the serum
will be collected and snap frozen for analysis.
Immediately post-operatively, while in the recovery room, a second blood draw will be performed
and the sample likewise sent to DCI for processing. A third and final 3cc specimen will be collected
at the two week routine follow-up appointment at which time a second questionnaire will be
completed. Group 2-4, Chronic pain, Fibromyalgia and Pelvic pain, patients will be identified at
the Anesthesia pain, Rheumatology and Gynecology clinic for eligibility for entry in the study
protocol. Those who meet criteria will complete the study questionnaire and undergo a single 3cc
blood draw. The blood will be collected in a 3cc purple top tube and transported to DCI for
processing. Samples will be labeled with a patient number and diagnosis. Group 5, Normal
controls, twenty normal control patients will fill out the study questionnaire and have a single
blood draw. The specimen will be collected in a 3cc purple top blood and processed in DCI.
Sample handling and determination of PCE activity: Samples will be collected, processed,
aliquoted in lOOuL fractions and stored at -70 in DCI. SchEs are extremely stable molecules so
short periods (<12hrs) between collection and processing should not interfere with measurements
of enzyme activity. 20.0uL of serum are added to 40.0uL of a 25% sucrose solution containing
lOmM Tris-formate (pH 9.0). 3.0uL are then separated by vertical flat bed polyacrylamide gel
electrophoresis on a 6.5% T: 5.0% C gel using a borate-sulfate discontinuous buffer system.
Following electrophoresis, the gel is equilibrated in 96mL Tris-chloride (pH 6.6) in the presence of
FAST Red TR or Fast BLUE RR as the diazonium salt for five minutes with gentle agitation. Add
4.0mL of 1.0% sodium alpha naphthyl acetate in acetone solution (the substrate) and allow the
reaction to proceed for ten minutes at room temperature with constant agitation. Stop the reaction
with 10% acetic acid. The resulting insoluble diazonium complex bands mark esterase activity.
Quantify the esterase activity by quantitative densitometry. Densitometric results are presented
as the integrated area under the curve of each peak expressed in pixels. The bench researcher will
have access to patient numbers only and will be unaware of the diagnosis. Results will be
tabulated in a password protected spreadsheet for statistical analysis after completion of specimen
collection.
72
Progress: Investigators are currently analyzing data for correlation between
pseudocholinesterase activity in pain patients compared to normal patients. In addition we are
optimizing the pseudocholinesterase activity assay and exploring other assays for determining
whether changes in activity are associated with changes in protein levels of pseudocholinesterase
or activation state. The protocol remains ongoing.
73
Detail Summary Sheet
Date: 30 Sep 06
Number: 203092
Status: Expired
Title: Animal Tissue Use in Biomedical Research and Training
Principal Investigator: MAJ Nancy L Merrill, VC
Department: Clinical Investigation
Facility: MAMC
Associate Investigator(s): None.
Start - Completion:
Funding:
Periodic Review:
7/13/2003 - Jul 2006
DCI
7/12/2006
Study Objective: To reduce live animal use in biomedical research or training at MAMC by
facilitating animal tissue use as alternative research/training models, wher feasible. Objectives
for individual projects proposed under this protocol will be defined in project addendum.
Technical Approach: In the past, personnel requesting authorization to conduct biomedical
research or training using postmortem animal tissues have been required by the MAMC IACUC to
submit a "stand alone" animal care and use protocol that describes the proposed tissue use,
background, justification, animal care provisions, literature searched conducted all in accordance
with federal animal welfare regulations. Many of the provisions and assurances contained in the
DoD-mandated animal use protocol format did not apply to research or training activities using
animal tissues only. The task of preparing full protocols and related animal use reports for such
activities places an unnecessary burden on individuals wishing to reduce live animal use by
justifiable utilization of animal tissues. The "alternative" use of postmortem animal tissues rather
than live animals (Reduction or Replacement) can be significantly facilitated by streamlining the
preparation, submission, tracking and reporting of such research or training activities under an
umbrella or stand protocol that spells out universal conditions for animal tissue use. and identfies
a Principal Investigator (PI) who is responsible for overseeeing these activities.
Progress: Two amendments were submitted during FY 2006 to collect tissue samples. Muscle
tissue samples were collected from animals undergoing IACUC approved terminal procedures.
Muscle tissue was used to test new tissue preservation media. Blood samples were collected as
non-terminal procedures from animals kept at DCI for training purposes. The blood samples were
used for combat casualty training in transfusion procedures in protocol 204058. Protocol expired as
of 12 Jul 2006.
74
Detail Summary Sheet
Date: 30 Sep 06 Number: 206109 Status: Ongoing
Title: Animal Tissue Use in Biomedical Research and Training
Principal Investigator: MAJ Nancy L Merrill, VC
Department: Clinical Investigation Facility: MAMC
Associate Investigator(s): CPT Joren B. Keylock, MC; James R. Wright, BA, MT (ASCP);
Donna J. Frey; CPT Matthew J. Eckert, MC
Start - Completion: Funding: Periodic Review:
7/12/2006 - Jul 2006 DCI N/A
Study Objective: To reduce live animal use in biomedical research or training at MAMC by
facilitating animal tissue use as alternative research/training models, where feasible. Objectives
for individual projects proposed under this protocol will be defined in project addendum.
Technical Approach: In the past, personnel requesting authorization to conduct biomedical
research or training using postmortem animal tissues have been required by the MAMC IACUC to
submit a "stand alone" animal care and use protocol that describes the proposed tissue use,
background, justification, animal care provisions, literature searched conducted all in accordance
with federal animal welfare regulations. Many of the provisions and assurances contained in the
DoD-mandated animal use protocol format did not apply to research or training activities using
animal tissues only. The task of preparing full protocols and related animal use reports for such
activities places an unnecessary burden on individuals wishing to reduce live animal use by
justifiable utilization of animal tissues. The "alternative" use of postmortem animal tissues rather
than live animals (Reduction or Replacement) can be significantly facilitated by streamlining the
preparation, submission, tracking and reporting of such research or training activities under an
umbrella or stand protocol that spells out universal conditions for animal tissue use and identifies
a Principal Investigator (PI) who is responsible for overseeing these activities.
Progress: Two amendments were submitted for tissue collection from other IACUC approved
terminal training protocols. One was for muscle tissue to test transport medium under different
conditions and the other was for arteries, veins, hearts, and eyes to be used to train surgical and
ophthalmological residents in various techniques specific to their specialties.
75
Detail Summary Sheet
Date: 30 Sep 06 Number: 203076
Status: Terminated
Title: Breeding Colony of Red-Spotted Newt (Notophthalmus viridescens)
Principal Investigator: MAJ Nancy L Merrill, VC
Department: Clinical Investigation
Facility: MAMC
Associate Investigator(s): CPT Patrick M. McNutt, MS; Steven O. Gibson
Montminy
; SPC Timothy S.
Start - Completion: Funding:
5/21/2003 - Jun 2006 DCI
Periodic Review:
5/11/2005
Study Objective: To provide newts of the appropriate type and age to meet the needs of IACUC
approved protocols.
Technical Approach: Newts will be purchased for the breeding colony and raised in an aquarium
or polycarbonate cages with lids to prevent escape. Newts will be provided an environment that is
mostly water but will have areas to leave the water, hide and interact with each other. Breeding
can be controlled based on the number of animals in each container and the temperature of the
water. Newts normally breed in the fall and winter when the water is colder. Thus by regulating
the water temperature up or down by a few degrees, mating behavior can be altered to regulate
offspring production. Eggs will be removed from the adult containers to prevent them from being
eaten. Eggs may then be used for some studies while others will be allowed to continue to develop
into adults for use as breeders or for other IACUC approved protocols. The larva are terrestrial
and will be housed in polycarbonate cages with plant material.
The tracking and accounting of each animal will be part of the daily colony management. Each
animal entering the colony, whether purchased or propagated, will be assigned an identification
number. The animal will be tracked as it is introduced into the breeding colony, transferred to an
experimental protocol, culled as excess to experimental requirements, or lost perinatally. Only the
breeding stock and animals culled as excess or lost perinatally will count against the breeding
protocol. All animals transferred to an experimental or training protocol will be counted against
that protocol. At 4 to 5 years of age, breeders will be euthanized and replaced with new breeding
stock. New breeding stock will be raised for replacement of breeding stock along the way. Newts
can have a long lifespan but it is not uncommon to have many lost younger due to escaping into an
area where they become dessicated and the fact that newts are very susceptible to any toxic
substances.
Progress: Notophthalmus viridescens did produce viable eggs for protocol #203122.
76
Detail Summary Sheet
Date: 30 Sep 06 Number: 206091
Status: Ongoing
Title: MAMC Rodent and Rabbit Quality Assurance and Sentinel Program
Principal Investigator: MAJ Nancy L Merrill, VC
Department: Clinical Investigation
Facility: MAMC
Associate Investigator(s): MSG Karen L Van Loon; SGT Anita J S Teadt;
Phillips; SPC Shayla M Phyall; Shelley L Spahn-Bridges; Jennifer L. Theis
SPC Miemie T
Start - Completion: Funding:
5/10/2006 - May 2009 DCI
Periodic Review:
N/A
Study Objective: The purpose of this protocol is to provide a reliable program for preventing the
introduction of adventitious organisms into the MAMC rodent and rabbit colonies. This will be
accomplished by sampling species from selected sources as they are received into the facility.
Suspect groups of animals will be quarantined based on vendor health reports, and their release
from quarantine will depend on results of quality assurance tests. Continuous health monitoring
or surveillance will be accomplished by housing sentinel animals in the animal rooms, and then
periodically submitting them for quality assurance testing.
Technical Approach: Experiment 1: Sentinel Surveillance: Sentinel animals must be of known
health status as indicated below in para. V.3.3.7. For this purpose, sentinel mice will be purchased
from JAX or Harlan and sentinel rats from JAX or Harlan. Sentinels will be kept in the colony at
least one month before they are sacrificed and tested, allowing for any potential exposures and
subsequent seroconversion to occur. Complete procedural techniques are outlined in LARS Quality
Assurance of Rabbits and Rodents and Sentinel Surveillance SOPs.
a. Mice: A minimum of 16 mice, 4 cages of 4 mice per cage, will be placed in each
occupied mouse room initially (preferably at the beginning of the calendar year). During cage
changing soiled bedding will be collected from at least 2-3 cages off of each rack in the room and
placed in a clean container and well mixed. The sentinel animals will be changed last. A handful
of the mixed dirty bedding will be broadcast over the clean bedding of a fresh cage before adding
the sentinel animals to the cage. Sentinel cages will be unfiltered, as open to the room as possible.
One cage of mice will be sacrificed each quarter. At the mid-point of the quarter, 2 of 4 mice in the
cage will be sacrificed for serology screening. The blood will be pooled from those 2 animals and
sent to Research Animal Diagnostic Laboratory (RADIL), University of Missouri. At the end of the
quarter, the remaining 2 mice will be sacrificed for comprehensive testing to include serology and
pathology by RADIL and in-house parasitology (including examination of pelts for external
parasites). Feces from each room will be pooled every six weeks and submitted for Helicobacter
testing by RADIL.
1) Should any rooms be used for breeding, sentinel mice will be selected from the indigenous
population. Retired breeders will be used for serology, whereas parasitology and pathology will be
performed on weanlings and young adults.
2) Extra animals (2 perl6 animals) will be ordered with each sentinel purchase, if not from
JAX or Harlan. See section V.1.2 These animals will be sacrificed within one day of delivery and
submitted for Quality Assurance Procedures described in para. V.4.4.2.
b. Rats: Sentinel rats will be managed in a similar manner, except they may be
housed singly. For long-term housing of rats (greater than two months), two sentinel rats will be
added to each occupied rat room initially. The cages will contain a sample of soiled bedding from
each rack of animals in the room each time the cages are changed, similar to the procedures for
changing mice. At the mid-point of the quarter 1 rat will be sacrificed for serology and
parasitology, and 1 rat will be sacrificed for a comprehensive pathologic examination, serology and
parasitology at the end of the quarter. Feces from each room will be pooled every six weeks for
floatation and testing for Helicobacter. One additional rat will be ordered with each sentinel rat
77
purchase. This animal will be sacrificed within one day of delivery and submitted for Quality
Assurance Procedures described in V.4.4.2.
c. In the face of a potential infectious disease outbreak, these sampling timetables
are compressed under the direction of the Chief, Laboratory Animal Resources Service, and are
based on pathogenesis of the suspected agents.
Experiment 2: Quality Assurance Sampling: For the approved vendors (Harlan and Jackson Labs),
the Chief, LARS will review and sign diagnostic health reports for the incoming shipment to
ensure that the incoming animals are free of adventitious organisms. These reports must be
current within six months. For other vendors, quality assurance will be performed on animals from
the same barrier and/or species/strain as those ordered.
In the event that animals from any approved vendors are found to be the source of an adventitious
organism within the animal colony, two extra mice/rats will be ordered with each shipment and
processed for QA testing until it is determined that additional testing is no longer necessary. This
determination will be based upon a current literature review of the epidemiology and
pathophysiology of the individual organism(s) in question.
If rodents or rabbits are received from an unknown vendor, they must have a diagnostic health
report current within six months. For these unknown vendors, additional animals (a minimum of
3-5%, but not less than two animals, at the discretion of the Chief, LARS, of the same strain,
facility, and barrier/location will be ordered with each shipment and will be submitted for quality
assurance testing. The Chief, LARS will base his/her decision upon a current literature review of
the epidemiology and pathophysiology of the individual organism(s) in question and upon current
quality assurance standards within the industry.
Data Analysis: Statistical analysis will not be necessary in this protocol. Results of serology,
parasitology, and pathologic examination will be used to determine whether or not adventitious
organisms enter the animal colony, their spread, and whether control measures are effective in
preventing and eliminating these agents.
Progress: Four C57BL were placed as sentinels in the mouse holding room. Two were submitted
for analysis and found negative for pathogens. Eight DBA/2 were placed in the nude mouse room.
Two were submitted for analysis and came back positive for a newly identified virus, Murine
Norovirus (MNV). This finding was discussed with the supplier and their colony has been found to
be positive for this non-pathogenic virus in immunocompetent mice. Transmission to the nude
mice is unlikely given methods of husbandry. A new source for sentinels will be identified for
future use.
78
Detail Summary Sheet
Date: 30 Sep 06 Number: 203075
Status: Terminated
Title: Mouse (Mus Musculus) Breeding Protocol
Principal Investigator: MAJ Nancy L Merrill, VC
Department: Clinical Investigation
Facility: MAMC
Associate Investigator(s): CPT Patrick M. McNutt, MS; Steven O. Gibson
Montminy
; SPC Timothy S.
Start - Completion: Funding:
5/21/2003 - May 2006 DCI
Periodic Review:
5/11/2005
Study Objective: To establish a breeding colony of mice for future use in research protocols.
Technical Approach: LacZ+ and normal mice will be purchased from Jackson Labs (a
commercial vendor with an established health monitoring history) to establish the breeding
colonies. The colony will start with up to 6 females and 3 males of each strain. The female mice
will be housed in groups when they are not pregnant or nursing pups. After they are used as
breeders for the first time, the male mice will be group housed except when paired with females for
mating. Propagation will be carefully managed: breeders will be paired only when there is a need
for offspring for an experimental protocol. Excess offspring not needed for the experimental
protocol for which they were bred will be transferred to other experimental or training protocols
when possible, used as sentinels or replacement breeders. If mice are not needed for any other
protocols, the excess offspring will be euthanized and tissues from these excess offspring will be
made available to other investigators for use on approved research. When mice are required for
use on an approved protocol, male and female(s) of the desired strain or stock will be housed
together for approximately one week and then separated. The female mouse will be provided with
nesting material in addition to the normal bedding used. The offspring will remain in the cage
with the female until they are used in an experimental protocol, culled, or weaned at
approximately 21 days of age. After the pups are removed, the female will be returned to pair
housing as soon as possible. Records will be maintained to show the breeding history of each
animal, i.e., which animals were paired, dates pairs were put together and separated, date of birth,
number of pups produced, number lost perinatally, number euthanized, etc. The tracking and
accounting of each animal will be part of the daily colony management. Each animal entering the
colony, whether purchased or propagated, will be assigned an ID number. Only the breeding stock
and animals culled as excess or lost perinatally will count against the breeding protocol. All
animals transferred to an experimental or training protocol will be counted against that protocol.
At 12 to 18 months of age, breeders will be euthanized and replaced with new breeding stock.
Additionally, if we identify female breeders that are unable to effectively rear their pups, these
animals may be euthanized prior to the stated ages. Breeders can be either homozygous or
heterozygous: thus, progeny need to be tested by a simple enzyme assay (performed on tail/ear
punches in our laboratory) for the presence of the LacZ enzyme. Negative homogozygotes can be
incorporated in the concurrent wild-type colony. The total number of experimental animals
initially requested on the protocol is 250/yr for three years (200 research subjects and 50 breeding
animals/strain). The mothering ability of the females of both strains is excellent and Jackson Labs
reports neonatal mortality to be less than 5%. If the percentage of pups that die or are euthanized
exceeds 20% this will be reported to the IACUC. If different stocks or strains are required for
protocols subsequently approved by the IACUC, additional animals will be requested by an
amendment to this protocol or by separate protocol.
Progress: Breeding colony started with 29 mice and 14 wild type were purchased to maintain
colony. A total of 315 wild type mice and 35 Rosa mice were weaned and transferred to protocol
205080.
79
Detail Summary Sheets
Hospital Dental Clinic
80
Detail Summary Sheet
Date: 30 Sep 06 Number: 203116 Status: Ongoing
Title: Host Response Gene 203014 in Military Populations
Principal Investigator: MAJ Scott W. Burgan, DC
Department: Dentistry Facility: MAMC
Associate Investigator(s): LTC Paul 0. Francis, DC; Richard P. Darveau, Ph.D.; MAJ Douglas
R. Dixon, D.M.D., M.S.D; COL (Ret) Robert B. O'Neal, DMD, MEd, MS; LTC Edward B. Fowler,
DC; Frank A. Roberts, D.D.S., Ph.D.; Beverly Dale, Ph.D.
Start - Completion: Funding: Periodic Review:
9/12/2003 - Sep 2007 DCI 8/29/2006
Study Objective: To determine the incidence of polymorphisms (mutations) in bacterial receptors
between periodontitis-affected and periodontally healthy dental patients.
Technical Approach: This study will look at a single nucleotide polymorphisms (SNP's) found in
hTLR and other host response genes that will be examined for their association with periodontitis
in the Hispanic and African American military population. Approximately 450 patients will be
enrolled in this study here at MAMC 225 periodontically healthy and 225 periodontitis-affected
that are 18 years of age and older. The frequency of different TLR pleomorphisms found in the
populations will be determined for their association to periodontitis using genomic DNA isolated
from cheek swab samples and compared for binomial proportions in periodontally healthy and
diseased subjects. This information will aid the army in identifying those individuals at risk for
developing periodontitis and will contribute to better health care by providing new information
concerning the molecular basis of increased susceptibility to and severity of periodontal disease.
Progress: This protocol remains ongoing with only 30 samples gathered during FY06. The
continuing challenge is in having personnel for sample gathering. With the high OPS Tempo at
Fort Lewis priorities have often been in other areas. There has also been a loss of some personnel
from the UW side of the house. The nature of this study is such that there is no problem with an
extended period of sample gathering. It is taking longer than anticipated but is still a viable and
important study to continue.
81
Detail Summary Sheets
Department of Emergency Medicine
82
Detail Summary Sheet
Date: 30 Sep 06 Number: 204087 Status: Terminated
Title: A Prospective Study on the Effects of Ginkgo Biloba on Bleeding Times
Principal Investigator: MAJ Jimmy L. Cooper, MC
Department: Emergency Medicine Facility: MAMC
Associate Investigator(s): MAJ Wesley G. Zeger, MC; Benjamin B. Betteridge, MD
Start - Completion: Funding: Periodic Review:
9/14/2004 - Jul 2004 DCI 6/28/2005
Study Objective: To determine if gingko biloba significantly affects the bleeding times in young
healthy volunteers.
Technical Approach: Twelve healthy volunteers will be enrolled in this prospective study. Each
subject will serve as their own control. Baseline bleeding times will be drawn using the Simplate
test procedure. Each subject will take gingko biloba for one week and then have a repeat bleeding
time done. This data will then be analyzed using the pair t-test to determine if gingko biloba
significantly affects bleeding times.
Progress: The protocol was eventually terminated by the Chief, Department of Emergency
Medicine in June 2006, as the Simplate test procedure was discontinued at MAMC and it was no
longer feasible to conduct the study. Four subjects were enrolled during FY05.
83
Detail Summary Sheet
Date: 30 Sep 06 Number: 206063 Status: Ongoing
Title: A Randomized Study of Capnography in Emergency Department Procedural Sedation
Principal Investigator: MAJ Mark A. Denny, MC
Department: Emergency Medicine Facility: MAMC
Associate Investigator(s): CPT Joseph P. Mazzoncini, MC; LTC David A. Della-Giustina, MC
Start - Completion: Funding: Periodic Review:
6/7/2006 - Apr 2007 Oridion via The Geneva Foundation N/A
Study Objective: To determine if capnographic data recognizes respiratory depression during
emergency department sedations that are not clinically recognized and whether these events are
clinically important.
Technical Approach: This study is a prospective, blinded, randomized trial evaluating
emergency physicians' use of capnography during consecutive procedural sedations on patients
who sign informed consent to participate. Approximately 22 emergency physicians would be asked
to consent for this trial. The physician may or may not have access to the capnographic data with
each sedation. The physician will then complete the sedation as typical. The emergency physician
should continuously evaluate the patient during the sedation as they normally would, however, if
not blinded to the capnographic data, they may use this to assist in their decision making
processes. The nurse observing the sedation will record the time to recovery and have the patient
fill out the visual analog scales evaluating injection pain recall, procedural recall, and patient
satisfaction. The physician completing the sedation will record, level of sedation, number of
clinically recognized respiratory depression events, recognized complications, clinician
interventions, and physician satisfaction. Study investigator will analyze the stored capnographic
data looking for unrecognized complications and respiratory depression events. The groups will be
compared by complication rates, incidence of interventions, incidence of respiratory depression
events, level of sedation, time to recovery, injection pain, procedural recall, physician satisfaction,
and patient satisfaction. A p-value of less than 0.05 will be considered statistically significant.
Data will be analyzed using chi square, ANOVA, Kruskal-Wallis, and Mann- Whitney U-test
methods.
Progress: This protocol is open to enrollment, with no patients enrolled during FY06. The data
recording device is not functioning properly and has been sent back to the manufacturer.
Enrollment will be initiated when the data recording device is working.
84
Detail Summary Sheet
Date: 30 Sep 06 Number: 206050 Status: Terminated
Title: Magnesium Sulfate for the Prevention of Etomidate Induced Myoclonus in Emergency
Department Procedural Sedation
Principal Investigator: MAJ Mark A. Denny, MC
Department: Emergency Medicine Facility: MAMC
Associate Investigator(s): CPT Joseph P. Mazzoncini, MC; LTC Benjamin P. Harrison, MC;
CPT Joshua A. Carr, MC
Start - Completion: Funding: Periodic Review:
Never approved Oridion via The Geneva Foundation N/A
Study Objective: To determine if pretreatment with magnesium sulfate is effective in preventing
etomidate induced myoclonus during emergency department procedural sedation. To determine if
capnographic data recognizes complications during emergency department sedations that are not
clinically recognized and whether these events are clinically important.
Technical Approach: This study is a prospective, double-blind, placebo-controlled trial
evaluating the usefulness of pretreatment with magnesium sulfate to reduce myoclonus induced
by etomidate sedation in emergency department patients 18 years of age or older who need
procedural sedation. Patients will be randomized to two groups of 58 patients each. The clinicians
will be randomized to be blinded or not to capnographic data. Patients will receive either placebo
or magnesium sulfate ninety seconds prior to sedation with etomidate. The nurse observing the
sedation will record the time to recovery and have the patient fill out the visual analog scales
evaluating injection pain recall, procedural recall, and patient satisfaction. The physician
completing the sedation will record myoclonus incidence, level of myoclonus, level of sedation,
recognized complications, unrecognized complications, clinician interventions, and physician
satisfaction. The groups will be compared by percentage of myoclonus, level of myoclonus (mild,
moderate, severe), level of sedation, time to recovery, complication rates, intervention rates,
etomidate injection pain, procedural recall, physician satisfaction, and patient satisfaction. A p-
value of less than 0.05 will be considered statistically significant. Data will be analyzed using chi
square, ANOVA, Kruskal-Wallis, and Mann-Whitney U-test methods.
Progress: Soon after initial IRB approval with stipulations January 2006, the PI terminated this
study due to issues with administration of Magnesium IV push when it was determined not to be
feasible clinically.
85
Detail Summary Sheet
Date: 30 Sep 06 Number: 206028 Status: Completed
Title: Application of the Wells Criteria to determine Pretest Probability of Pulmonary
Embolism: A Retrospective Review of the practices of the Madigan Army Medical Center
Department of Emergency Medicine
Principal Investigator: CPT Gregory M. Johnston, MC
Department: Emergency Medicine
Facility: MAMC
Associate Investigator(s): CPT Phu Tan Nguyen, MC; LTC Benjamin P. Harrison, MC
Start - Completion:
12/14/2005 - Mar 2006
Funding: Periodic Review:
DCI N/A
Study Objective: To determine if MAMC emergency residents/staff are making use of explicit
criteria, i.e. Wells criteria, versus utilizing an empirical method, i.e. drawing upon past experience,
when determining the pretest probability of pulmonary embolism and to enhance awareness of the
clinical utility of the Wells criteria, and thereby optimize the care of patients by preventing the use
of inappropriate diagnostic tests.
Technical Approach: Emergency Department charts will be inspected for the presence of a
history of the present illness (to account for immobilization, or hemoptysis), vital signs (to account
for heart rate), past medical history (to account for malignancy, previous deep venous thrombosis
or pulmonary embolism, or recent surgical intervention), and physical exam (to account for the
presence of suspected deep venous thrombosis)-all noted components of the Wells criteria. It is
imperative to note that charts lacking any of these findings will be considered empirically
assessed.
Progress: This protocol was reported completed in June 2006. To date, 300 charts met all
inclusion criteria for the study; 24 cases of deviation from appropriate risk stratification were
identified: 8% empiric risk stratification:
5 with positive d-dimer and no follow-up study (none of patients signed out AMA)
9 with low pre-test probability that went straight to CTPA; 1 with positive CTPA for PE: 37.5%
8 with moderate pretest probability that underwent d-dimer testing prior to CTPA: 33%
2 with moderate pretest probability with d-dimer testing (all negative) and no additional testing
Of the 300 charts reviewed, a total of 24 documented cases of pulmonary embolism were noted. Of
the 24 cases, 4 were inappropriately risk stratified-with 2 of the 4 cases experiencing a delay in
disposition secondary to inappropriate risk stratification. The PI noted that this is preliminary
data that is subject to additional analysis before conclusions can be drawn. It can be confidently
posited, however, that the data indicates that additional resident education would prove to be
beneficial.
86
Detail Summary Sheet
Date: 30 Sep 06 Number: 206059 Status: Ongoing
Title: Causes and consequences of patients who left a busy Army Medical Center Emergency
Department prior to evaluation by a qualified health care provider
Principal Investigator: CPT Adam S. Nielson, MC
Department: Emergency Medicine Facility: MAMC
Associate Investigator(s): Christopher S. Kang, MD
Start - Completion: Funding: Periodic Review:
1/31/2006 - Mar 2006 DCI N/A
Study Objective: The purpose of this study is to, first, describe the characteristics if the large
number of patients who register for care at the MAMC- ED, then subsequently leave prior to
evaluation by a qualified provider. Describing the characteristics of these patients should help
identify where the MAMC health care system can make quality improvement changes to improve
patient health care and access to a qualified provider. Secondly, the nature of the acuity of the
illnesses or injuries that this population of patients represents will be described to determine if
patients with severe illness are being permitted to leave prior to evaluation, subjecting the
hospital and it's providers to unnecessary liability. Patients will be contacted to determine the
outcomes of their illnesses; i.e., did the patients seek care elsewhere, return to the MAMC-ED,
hospitalized, or did the illness/injury improve on its own.
Technical Approach: Patients who leave the Madigan Army Medical Center-Department of
Emergency Medicine, prior to being evaluated will be contacted by phone by the investigators and
asked a standardized series of questions regarding the nature of their illness, what they have done
to address it, why they left the emergency department prior to formal evaluation, and what could
have been done to prevent their leaving.
Progress: Nearly 200 patients participated in this protocol; although less than the original goal,
the current number is larger than past studies both referenced and/or reviewed. Data analysis will
be initiated to see if statistical significance has been achieved or whether or not the study should
resume. A more accurate assessment should be available by the end of the year.
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Detail Summary Sheet
Date: 30 Sep 06 Number: 206078 Status: Ongoing
Title: Emergency Medicine/Combat Trauma Management Training Using Animal Models
(Domestic Goat/ Capra hircus, Pig/Sus scrofa)
Principal Investigator: MAJ Bradley N. Younggren, MC
Department: Emergency Medicine Facility: MAMC
Associate Investigator(s): LTC Benjamin P. Harrison, MC; MAJ Brandon K. Wills, MC;
Christopher S. Kang, MD; MAJ Robert B. Blankenship, MC; MAJ Melissa L. Givens, MC; CPT
Jacob A. Roberts, MC; CPT Todd F. Baker, MC
Start - Completion: Funding: Periodic Review:
4/12/2006 - Mar 2009 DCI N/A
Study Objective: To effectively train providers combat-relevant resuscitative skills, focusing on
preservation of life, limb, critical organ function, and casualty stabilization.
Technical Approach: Training will utilize both inanimate (e.g. mannequin, cadaver, Sim Man,
etc.) and live, anesthetized animal models. Whenever feasible, inanimate models will be used in
place of live animals. Animal species used for this protocol will include goat and pig.
Progress: Three training labs were held in FY 2006, using 18 animal models and training 84
emergency medicine residents in emergency medicine and combat casualty procedures. Training
is further enhanced by the use of simulation models at the Anderson Simulation Center. During
the course of a three year residency, 1st year residents progress from trainees to instructors by
their 3rd year. Residents graduate with tangible improvement of skills necessary to perform
emergency medicine and combat casualty procedures.
88
Detail Summary Sheets
Department of Family Medicine
89
Detail Summary Sheet
Date: 30 Sep 06 Number: 205133 Status: Ongoing
Title: Prevalence of Hypertension in Active Duty Service Members
Principal Investigator: COL Gary W. Clark, MC
Department: Family Medicine Facility: MAMC
Associate Investigator(s): LCDR Brian A. Smoley, MC, USN
Start - Completion: Funding: Periodic Review:
9/7/2005 - Dec 2005 DCI 8/14/2006
Study Objective: To use screening blood pressure measurements collected during mandatory
wellness screenings to estimate the prevalence of hypertension in a population of active duty
service members at Fort Lewis.
Technical Approach: This will be a retrospective, cross-sectional analysis of data collected on
approximately 10,000 active duty service members who presented for wellness screenings through
the I Corps Readiness and Outcomes Wellness Service (ICROWS) between January 1 and
December 31, 2004. Data on measured blood pressure and self-reported age, rank, gender,
race/ethnicity, and use of blood pressure medications will be collected from the ICROWS database
without any inclusion of or reference to individual identifying information. Measured blood
pressure and self-reported use of blood pressure medications will be used to estimate the
prevalence of hypertension in the study population. Age-specific and age-adjusted prevalence of
hypertension will be reported using descriptive statistics. Relationships between hypertension and
demographic variables will be explored through bivariate and/or multivariate analyses.
Progress: Data on 15,391 study subjects has been analysed to estimate the prevalence of
hypterension in the study population. A draft of the analysis is currently undergoing AMEDD
public affairs review prior to being submitted for credit toward completion of a MPH degree at the
University of Washington. The researchers anticipate keeping the protocol open for an additional
year in order to allow for potential protocol modifications involving the collection of additional data
to facilitate secondary analyses. Presentation of the results and/or submission for publication in a
peer-reviewed journal are anticipated within the year.
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Detail Summary Sheet
Date: 30 Sep 06
Number: 205124
Status: Ongoing
Title: Racial Differences in Health Outcomes for Adults with Diabetes
in a Military Setting
Principal Investigator: LTC Telita Crosland, MC
Department: Family Medicine
Facility: MAMC
Associate Investigator(s): None.
Start - Completion:
8/23/2005 - Jul 2006
Funding:
DCI
Periodic Review:
8/10/2006
Study Objective: To evaluate health outcomes for diabetic patients based on race in a military
setting.
Technical Approach: This study is a quantitative cross-sectional analysis of approximately 5000
adult patients in the MAMC diabetic database. Data to be recorded inlcudes: race, age, rank, low
density lipoproteins, hemoglobin AlC, blood pressure, micro albumin, and number of clinic visits.
Descriptive statistical analysis will be used to determine if there is a statistical and clinical
difference in health outcomes in the diabetic patient based on age.
Progress: This protocol has completed data collection and analysis, but remains ongoing to
complete final manuscript.
91
Detail Summary Sheet
Date: 30 Sep 06 Number: 204117 Status: Ongoing
Title: Impact of the Sole Prescriber Program on use of Opioid Medications and Quality of Life
Principal Investigator: COL Diane M. Flynn, MC
Department: Family Medicine Facility: MAMC
Associate Investigator(s): COL Guy P. Runkle, MC; Steven J. Konicek, MD; Nancy A.
Poffenberger, PAC, Ph; Claudia N. Swenson, PhD; Gary J. Revello, RPh; Helen E. Holt, ARNP;
LTC Mary T. Bennett, AN; MAJ Elizabeth C. Shanley, MC
Start - Completion: Funding: Periodic Review:
8/31/2004 - Dec 2004 DCI 8/14/2006
Study Objective: This protocol is designed to determine if enrollment of Madigan patients
identified as being high utilizers of narcotic medication into a sole prescriber program results in a
decrease in escalation of narcotic use and an improvement in patient satisfaction. Secondary
objectives include determination of the impact of the sole prescriber program on continuity of care,
utilization of services and quality of life.
Technical Approach: An estimated 50 MAMC patients who have received more than 7
prescriptions from the MAMC pharmacy for opioid medications per quarter during all of the first
three quarters of FY2004 will be randomized into two groups: (1) immediate and (2) delayed
enrollment in the Sole Prescriber Program. Patients randomized for immediate enrollment will be
enrolled starting 1 October 2004. Delayed enrollment will begin 1 February 2005. The groups will
be compared with regard to monthly dosage of opiod medications expressed in morphine
equivalent dosage, number of prescribers of narcotics per patient, and several measures of
utilization of clinical services. In addition, patient satisfaction and quality of life will be measured
at baseline and after three months in both groups.
The following dependent variables will be compared between study groups using the paired t-test:
(1) Change in morphine equivalent dosage of narcotics, (2) Mean number of prescriptions for
narcotics per patient per quarter, (3) Mean number of prescribers of narcotics per patient per
quarter, (4) Mean number of ER visits per patient per quarter, (5) Mean total MAMC visits per
patient per quarter, (6) Mean total visits to health care facilities in community billed to TRICARE
per patient per quarter, and (7) Score on quality of life survey. The following binary dependent
variables will be compared between study groups using the McNemar's test: (1) At least one visit
to primary care provider per quarter (Yes/No), and (2) Is a narcotic agreement recorded in the
electronic medical record (Yes/No). The 5-item patient satisfaction survey will be analyzed using
the Wilcoxin- Signed rank test.
Progress: Investigators have performed initial analysis of results on 16 subjects, but have not yet
performed statistical analysis. The protocol remains ongoing to complete analysis and final write
up.
92
Detail Summary Sheet
Date: 30 Sep 06 Number: 206105 Status: Ongoing
Title: Implementation of an Office-Based Screening Tool to Improve Adherence with
Recommended Preventive Services in Primary Care
Principal Investigator: COL Diane M. Flynn, MC
Department: Family Medicine Facility: MAMC
Associate Investigator(s): COL Gary W. Clark, MC; MAJ Ross E. Colt, MC; LTC Kathryn K.
Ellis, MC; CPT Andrea S. Otto, MC; Janet 0. Schertzer; John G. Meyer, MD
Start - Completion: Funding: Periodic Review:
7/5/2006 - Dec 2007 DCI N/A
Study Objective: To determine if the use of a questionnaire and written instructions at every
primary care visit to assess adherence with recommended preventive services will increase rates of
recommended preventive services.
Technical Approach: Beginning 1 July 2006, all patients presenting for care at Madigan Family
Medicine Clinics will be asked to complete a preventive services checklist to determine if they are
up to date on recommended preventive services. The nurse or nursing assistant who screens the
patient will assist the patient in completing the questionnaire as needed, will distribute
appropriate educational materials as indicated and will order indicated labs and studies under the
primary care provider's name. The provider who sees the patient will perform any indicated
examination and order any indicated labs or studies as time permits. If time does not permit
addressing preventive services, the patient will be instructed to make a follow up appointment for
a periodic physical examination. Rates of adherence with recommended preventive services will be
compared between the pre-intervention and post-intervention periods between patients seen in the
Gold Team and those seen in other Family Medicine Clinic teams. Data will be prepared by the
Health Outcomes section and will be devoid of patient identifiers.
Progress: This protocol began enrollment on 11 Sep 2006. Since that date, front desk clerks have
been instructed to distribute the screening questionnaire to all adult patients who seek care on the
Family Medicine Clinic Gold Team (exclusive of sick call patients).
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Detail Summary Sheet
Date: 30 Sep 06 Number: 205130
Status: Ongoing
Title: Use of Pedometers Among Healthcare Providers in a Large Military Family Medicine
Department
Principal Investigator: CPT Kevin M. Kelly, MC
Department: Family Medicine
Facility: MAMC
Associate Investigator(s): MAJ Robert C. Oh, MC; MAJ Alvin Y. Tiu, MC
Crosland, MC; CPT Jarret E. Sands, MC
; LTC Telita
Start - Completion: Funding:
8/30/2005 - Aug 2006 DCI
Periodic Review:
8/29/2006
Study Objective: To determine the affect of a pedometer exercise program on the level of physical
activity of health care providers in a primary care clinic.
Technical Approach: This study sets out to determine the affect of a pedometer exercise
program on the level of physical activity of health care providers in a primary care clinic.
Residents, faculty, and mid-level providers in the MAMC Family Medicine Department,
approximately seventy total subjects, will be enrolled in the study. Study subjects will be
evaluated for baseline physical activity level category with the International Physical Activity
Questionnaire (IPAQ) and baseline daily step count. They will be given a pedometer and
instructions on increasing their daily activity level. Their daily step count will be followed for six
weeks. The IPAQ will be repeated post intervention. A pre and post intervention BMI and blood
pressure will be also measured. The change in number of steps taken per day, METS/day, and
physical activity category (sedentary, low active, somewhat active, active, highly active) will be
statistically analyzed correlated to independent variables of age, BMI, and blood pressure.
Differences between staff, residents, and mid-level providers will also be evaluated.
Progress: This protocol closed to enrollment with 50 providers (subjects) enrolled. The subjects
completed their six week pedometer course and returned their surveys and log books to the
principal investigator. The information has been entered into a database; study staff is in the
process of analyzing the data and writing up the project. No adverse events occurred. Anticipate
study completion within the next two months.
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Detail Summary Sheet
Date: 30 Sep 06 Number: 206019 Status: Completed
Title: Pediatric Obesity in a Military Family Medicine Clinic
Principal Investigator: LCDR Sandra L. Kimmer, MC
Department: Family Medicine Facility: MAMC
Associate Investigator(s): None.
Start - Completion: Funding: Periodic Review:
11/28/2005 - Aug 2006 DCI N/A
Study Objective: The specific aims of this study is to measure the prevalence of pediatric obesity
and overweight in children ages 6-11 enrolled at Madigan Army Medical Center Family Medicine
Clinic and to discover the relationship between pediatric obesity in this population and race,
sponsors active duty status, and socioeconomic status (SES) as measured by the sponsor's rank. An
additional phase of this study is to determine the percentage of those children who meet criteria
for obesity based on BMI for age that have not been formally diagnosed.
Technical Approach: ICDB records for all children who were age 6-11 and enrolled in the
Madigan Army Medical Center Family Medicine Clinic during 2004 will be reviewed. Because age,
sex, height, and weight are required to calculate the BMI percentile for age and sex and thus
determine whether or not a child is obese, only those children who had a clinic visit in 2004 during
which both height and weight were recorded will be selected for this study. If more than one visit
meets these criteria, data from the most recent visit only will be used to calculate the BMI percent
for age and sex.
Progress: This protocol was reported completed in July 2006. Excerpt of results:
Of the 668 subjects in the study cohort, 97 (14.5%) met the diagnostic criteria for obesity. An
additional 92 (13.8%) children were clinically overweight. The mean BMI% for the overweight and
obese children was 93.8% (SD=4.22). The average age for these children was 9.19 year (SD=1.67).
The one-sample binomial test was used to compare the 14.5% obesity rate found in this study to
the 15.3% rate reported among 6-11 year olds in the 1999-2000 NHANES study. These
percentages were not significantly different (p=.307). The prevalence of overweight (13.8%) was
also not significantly different from the 1999-2000 NHANES prevalence of 15% (p=.202).
The largest difference in weight status between the genders was seen in the overweight category.
Of the overweight children, 58 (63.0%) were male and 34 (36.9%) were female. Overall, males had
a 16.4% prevalence of overweight and a 14.7% prevalence of obesity. Female prevalence rates were
10.8% and 14.3% respectively. Chi-square analysis did not show a statistically significant
difference in overweight or obesity based on gender (p=.102). Almost 24% of 11 year olds in this
study were clinically obese. Overweight was highest among 10 year olds with 18.8% of the cohort
being clinically overweight. Increased age was the only independent variable to show a
statistically significant relationship to weight status (p=.017).
Of the 97 subjects who met the diagnostic criteria for obesity, only 12 had a formal diagnosis of
obesity on their medical record. Only one of the 92 overweight children was formally diagnosed.
This rate of diagnosis, 6.9% (13 out of 189 children), is significantly different from the 80%
diagnosis rate, which was considered acceptable (p<.001). The average BMI percentile for those
children diagnosed (98.3%, SD=1.52) was similar for males was (98.4%, SD=0.98) and females
(98.2%, SD=1.83). The mean BMI% for children diagnosed was higher than that of children who
met criteria for overweight or obesity but were not diagnosed (93.8%, SD=4.22). This difference in
BMI% was not statistically significant (p=.466)
95
More females were diagnosed (10.1%) than males (4.5%) although this difference was not
significant (p=.135). The association between the type of provider seen and whether or not the
overweight child was formally diagnosed approached significance (p=.076). More nurse
practitioners diagnosed overweight and obese children (16.1%) than physicians (7.8%) or
physician's assistants (3.1%). The frequency of visits to a provider did not impact whether or not
the diagnosis was made (p=.398). Although health problems are common in overweight children,
children in this cohort who met diagnostic criteria for overweight or obesity did not have
significantly more visits than their normal weight peers (p=.276).
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Detail Summary Sheet
Date: 30 Sep 06 Number: 206048 Status: Ongoing
Title: A Randomized, Controlled Trial of Manual/Manipulative Therapy for Acute Low Back
Pain in Active Duty Military Personnel: A Pilot Study
Principal Investigator: MAJ Douglas M. Maurer, MC
Department: Family Medicine Facility: MAMC
Associate Investigator(s): Scott T. Stoll, D.O., Ph.D.; MAJ Charles W. Webb, MC; CPT Jarret
E. Sands, MC; CPT April E. Lynch, MC; CPT Richard J. Geshel, MC; MAJ David L. Brown, MC;
CPT Hyrum F. Durtschi, MC; COL Gary W. Clark, MC; CPT Scott P Grogan, MC; Tonya N.
Kozminski, MD
Start - Completion: Funding: Periodic Review:
3/21/2006 - Feb 2007 Samueli Institute for Information Biology N/A
Study Objective: To evaluate the efficacy of conservative, non-surgical, manually applied
biomechanical treatments to reduce pain and improve function in young adult active duty military
personnel with acute low back pain.
Technical Approach: This is a prospective, randomized, blinded, controlled clinical trial that
plans to enrollment male and female Soldiers ages 18-25 consecutively from all military personnel
presenting during sick call to the Acute Care Clinic, Department of Family Medicine, Madigan
Army Medical Center, Fort Lewis, Washington. Informed consent will be obtained from the
subjects who desire to participate in the study by the Clinical Research Coordinator (CRC) and
assigned randomly to treatment (M/MT) or control (Standard Care) groups. The Study Evaluating
Physician (SEP) will perform a routine exam to address the exclusion criteria. If the patient is not
cleared for the study by the SEP s/he will enter routine care and be excluded from the study. If the
subject is cleared for the study by the SEP, the subject will be given an appointment with a Study
Treatment Provider (STP). The subject will be informed of the study group assignment and
treatment initiated. All subjects will be scheduled to see the same STP for all study treatment
visits. All subjects from both treatment and control groups will see the SEP for evaluation
regarding modified duty assignment. The SEP and CRC will be blinded to group assignment. For
this study, standard care will include prescribed medications including acetaminophen, ibuprofen
or naprosyn, cyclobenzaprine for up to one week; acetaminophen with codeine for up to 1 week;
passive modalities (ice, heat) for symptomatic relief; handouts on back self-care and exercises.
Subjects will be reevaluated at 2 weeks and 4 weeks for improvement. The treatment group will
receive manual/manipulative therapy (M/MT) in combination with standard care. M/MT involves a
set of treatments with elements of both osteopathic manipulative and chiropractic techniques and
sessions will be given up to twice a week for up to four weeks.
Pain will be measured using the Visual Analog Scale and quantification of medication use.
Functionality will be assessed using the Roland Morris Questionnaire, Back Pain Functional
Scale, and days on limited duty. Statistical analysis tools will include: descriptive statistics, cross
tabulations and measures of association, chi-square for dichotomous variables, and a 2x3 mixed
factorial ANOVA. Three one-way ANOVAs comparing the treatment groups on pain, functionality,
medication use and other outcome scores will be performed using residualized improvement scores.
Progress: This protocol remains open to enrollment, with a total of 12 patients enrolled during
FY06. All 12 patients received study treatment, but one patient failed to follow-up after the first
visit and has had no further data collected. The remaining eleven patients continued to be
followed. No adverse events have occurred. Enrollment will continue with the goal of 100 subjects
completing the study.
97
Detail Summary Sheet
Date: 30 Sep 06 Number: 205025 Status: Completed
Title: Prevalence of Vitamin B12 Deficiency in the Type 2 Diabetic Population
Principal Investigator: CPT Matthew C. Pflipsen, MC
Department: Family Medicine Facility: MAMC
Associate Investigator(s): MAJ Robert C. Oh, MC; MAJ Aaron A. Saguil, MC; CPT Derek K.
Seaquist, MC
Start - Completion: Funding: Periodic Review:
2/24/2005 - Dec 2005 DCI 1/4/2006
Study Objective: To determine the prevalence of B12 deficiency in Type 2 diabetics as
documented by (1) B12 levels <100pg/ml or (2) B12 levels of 100-350pg/ml plus elevations in serum
methylmalonic acid and homocysteine greater than 3 standard deviations above the mean of
normal subjects.
Technical Approach: The study population will include 200 consecutive Type 2 diabetic patients
older than 45 years of age presenting to the Family Medicine Clinic. Data on medication use, past
medical history, and nutrition will be obtained by a survey. Blood samples will be collected for
measurement of serum B12 levels. Measurement of serum methylmalonic acid and homocysteine
will be carried out on samples requiring further testing for diagnosis. Descriptive statistics will be
performed and associations between patients diagnosed with B12 deficiency and without B12
deficiency will be analyzed using the Chi-square test, Student t-test and multiple logistic
regression.
Progress: This protocol completed data collection during FY06, with 204 subjects enrolled; 199
who completed study participation. The principal investigator has left MAMC; he reports that
statistical analysis of the data remains ongoing. An abstract of findings was not available at the
time of this report.
98
Detail Summary Sheet
Date: 30 Sep 06 Number: 206067
Status: Completed
Title: Determinants of Military Medical Student Interest in
Principal Investigator: LTC Irene M. Rosen, MC
Family Medicine
Department: Family Medicine
Facility: MAMC
Associate Investigator(s): None.
Start - Completion: Funding:
3/27/2006 - Nov 2006 DCI
Periodic Review:
9/30/2006
Study Objective: To determine the factors which influence military medical students' interest or
lack of interest in the field of Family Medicine.
Technical Approach: A study questionnaire will be forwarded via electronic mail to all 3rd and
4th year medical students at the Uniformed Services University of the Health Sciences (USUHS)
as well as those participating in the Health Professions Scholarship Program (HPSP). The study
subjects will be asked for their cooperation with the questionnaire, informed that participation is
completely anonymous and voluntary, and asked to email their responses back to the investigator
who will collect and analyze all data.
Progress: Overall, 35 (11.3%) of survey respondents considered FM to be their specialty of choice
at the time of survey administration. Twenty (57%) of these students named FM as a specialty
they considered when entering medical school. The primary factors cited by students choosing FM
were lifestyle and flexibility (71%), personality fit (65%), job satisfaction (65%), continuity of care
(62%), diversity of patient population (59%), and the type of people who would be their future
colleagues (59%). This is in interesting contrast to students choosing general surgery and surgical
specialties, whose primary influencing factors were overall level of satisfaction (69%) frequency of
deployments (54%), amount of specialty bonus (45%), and opportunity to sub- specialize (38%).
Conclusion: This study shows that students choosing FM are motivated by different factors than
students choosing other specialties, and we may influence student recruitment by focusing on the
strengths of our specialty and highlighting these strengths during clinical rotations.
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Detail Summary Sheet
Date: 30 Sep 06
Number: 205103
Status: Completed
Title: The Role of Evidence and Other Determinants in Resident Discussions of Spirituality with
Patients
Principal Investigator: MAJ Aaron A. Saguil, MC
Department: Family Medicine
Facility: MAMC
Associate Investigator(s): None.
Start - Completion:
10/17/2005 - Mar 2006
Funding:
DCI
Periodic Review:
N/A
Study Objective: To determine which factors (including clinical evidence) are most likely to
predict whether a family medicine resident is likely to initiate a discussion of a patient's
spirituality. This study of family medicine residents seeks to (1) compare individual likelihood of
initiating discussions of spirituality vis-a-vis discussions of medications, (2) compare the Spiritual
Well-Being Scale (SWBS) scores (a validated surrogate for spirituality) of those more likely and
those not more likely to initiate discussions of spirituality when given evidence linking spirituality
with improved patient outcomes, and (3) analyze which demographic variables are significant
predictors of likelihood of initiating discussions.
Technical Approach: A survey containing the SWBS and questions querying demographic and
practice characteristics will be mailed to 750 family medicine residents (anticipated response rate
50%, or, 375 residents for ? = 0.80 at a p < 0.05). It will be mailed in three iterations to enhance
response. Primary data collected will look at resident likelihood of initiating discussions of
spirituality when presented with evidence linking spirituality with positive outcomes (which will
be compared in an analytic fashion against resident likelihood of initiating discussions of a new
medicine when presented with evidence linking the new medicine to positive outcomes); this data
will be analyzed using the Wilcoxon Signed-Ranks Test. Data will also be collected on the mean
SWBS score among those more likely and those not more likely to initiate spiritual discussions
with patients; this data will be analyzed with Analysis of Variance (ANOVA) testing. Finally, the
descriptive demographic data will be collected to see if any of these variables influence a family
medicine resident's likelihood of initiating spiritual discussions; these data will be analyzed using
multiple linear regression.
Progress: Results: Surveys from 385 of the 750 subjects were returned complete (51.3%). Twenty-
two surveys were excluded; the adjusted response rate was 49.8%. The sample was 53.9% female.
Approximately half of the respondents (48.9%) were over 30 years of age. Whites comprised 67.5%
of the sample, and non-Christian religious affiliation represented 26.2%. Geographic regions were
equally represented. Almost all residents (97.2%) said that they would discuss religion if requested
to do so by a patient. The majority (71.3%) either 'strongly' or 'moderately' agreed that they would
initiate discussions of spirituality more often if provided with good evidence that spirituality was
associated with good health. Geographic region (p=0.004), religion (p=0.005), and SWBS quartile
(p<0.001), were significant, independent predictors of 'strongly' agreeing that one would be more
likely to discuss spirituality. By subcategory, residents in the Northeast and Midwest were three
times more likely to initiate discussion than those in the West. Protestants were almost four times
more likely to do so that non- Christians. Residents in the lowest SWBS quartile were less likely to
discuss spirituality than those in the highest quartile.
When directly compared to likelihood of discussing a new medication, 56% agreed that they would
be at least as likely to discuss spirituality, given equal evidence for each. Region (p=0.002), religion
(0.002), and SWBS quartile (p<0.001) continued to be significant, independent predictors of being
as likely to discuss spirituality as a new medication. White respondents were less likely to discuss
100
spirituality than a medication, given equal evidence, than those in the 'Other' race category.
Residents training in the Northeast and Midwest had higher odds ratios for being as likely to
discuss spirituality as a medication than those in the West. Protestants and 'Other' Christians had
higher odds ratios for being as likely to discuss spirituality as a medication that non- Christians.
The average SWBS score for residents who were as likely to discuss spirituality as a medication
was 102.6 (SD 14.3), compared to 92.3 (SD 16.5) for those who were not (p<0.001).
Conclusions: Family medicine residents are willing to discuss spirituality if requested by patients
to do so. Additionally, given evidence, residents indicate that they are more likely to discuss
spirituality than they do currently. However, given equally robust evidence for each, few residents
indicated that they were as likely to start discussion of spirituality as they were a new medication.
Additional investigations are needed to determine the barriers that prevent the acceptance of
spirituality-related research.
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Detail Summary Sheet
Date: 30 Sep 06 Number: 206104 Status: Ongoing
Title: Implementing a Medical Ethics Curriculum in a Family Medicine Residency: Assessment
of Need, Description of the Process, and Evaluation of Effectiveness
Principal Investigator: LCDR Richard W. Sams, MC, USN
Department: Family Medicine Facility: MAMC
Associate Investigator(s): CPT Susan P. Opar, MC
Start - Completion: Funding: Periodic Review:
7/5/2006 - Jun 2007 DCI N/A
Study Objective: The objectives are: (1) to assess family medicine residents and staffs baseline
level of knowledge and comfort level in dealing with ethical issues in medicine, (2) to implement a
medical ethics curriculum in the family medicine residency, describe the curriculum's content and
implementation process and (3) to evaluate any gains in knowledge and comfort level from the
educational intervention and participants' perceived value of the curriculum.
Technical Approach: All faculty and residents will be invited by email (Attachment #1) and
announcements to participate in the study. They will be made aware that comparisons will be
made of their LNA and post-test curricular survey. The numbered LNA tool will be placed in their
mail boxes. They will be asked to return the completed tools to the associate investigator's
mailbox. The curriculum will be implemented by integrating each 45 minute seminar into the
already existing CME schedule. Four forty-five minute didactic sessions occur each Wednesday
morning for CME and GME. Once per rotation block, a medical ethics seminar will be conducted
by the PI during one of the four didactic sessions. The syllabus developed by the PI will serve as
the template for the sessions. All members of the faculty and residents are encouraged to attend
the CME lectures in general. At the one year mark the post-test curricular survey tool will be
placed in all faculty and residents mailboxes, and they will be asked to complete the survey at that
time. The post-test curricular surveys will have the same number for each person who completed
the LNA. This information will then be analyzed. See the attached curriculum, which contains the
syllabus, LNA and post- test / curricular survey.
The knowledge portion of the LNA and post-test consist of 10 multiple choice case-based questions,
with one correct answer for each question. Each case has a corresponding question regarding how
comfortable the person is with the described ethical dilemma and how to resolve it. The person is
to respond by rating his or her level of comfort on a 10 point Likert scale. The LNA and post-test /
curricular survey assesses the person's perceived value of the ethics training for preparing him or
her to address similar ethical issues. This is assessed on a 10 point Likert scale. The LNA tool
assesses how burdensome the LNA was to complete on a 10 point Likert scale. The post-test /
curricular survey also assesses the following: participants perceived value of the curriculum
personally and professionally; how many seminars were attended; and an assessment of was there
too little, too much or the right amount of emphasis on medical ethics.
Progress: A total of 40 participants enrolled, which included family medicine staff and residents.
Thirty of the 40 voluntarily and anonymously completed the learning needs assessment / pre-test.
The data from this instrument is currently being analyzed. Four educational sessions were
completed during the weekly continuing medical education time for the staff and residents.
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Detail Summary Sheet
Date: 30 Sep 06 Number: 205132
Status: Completed
Title: Colonoscopy by a Family Physician: A Case Series Demonstrating Healthcare Savings
Principal Investigator: MAJ Matthew W. Short, MC
Department: Family Medicine
Facility: MAMC
Associate Investigator(s): CPT Kevin M. Kelly, MC
Start - Completion: Funding:
9/1/2005 - Nov 2005 DCI
Periodic Review:
8/22/2006
Study Objective: To illustrate the potential cost savings to the military health care system by
implementing colonoscopy training in family medicine residency programs.
Technical Approach: A cost comparison/analysis will be done to show significant savings to the
TRICARE system by implementing colonoscopy training in family medicine residency programs.
Procedure reports will be reviewed on all 182 TRICARE beneficiaries receiving a colonoscopy at
Bayne- Jones Army Community Hospital, Fort Polk, LA performed by a credentialed family
physician between Sept 2003 and May 2005. Each procedure will be properly coded using the
standard CPT code for the procedure, anesthesia, and pathology specimens. Standard E&M codes
used by civilian gastroenterologists in the Louisiana community will also be included to determine
the total cost. All reimbursable codes for each patient will then be multiplied by the actual cost
billed to TRICARE in 2004 for the given procedures and outpatient visits. Data will show the total
cost savings to the military health care system by utilizing a single family physician to perform
colonoscopies one half day a week at Army community hospitals. Potential nation-wide yearly cost
savings to TRICARE for civilian gastroenterology colonoscopy referrals will then be determined
using the average colonoscopy cost and total number of civilian referrals in 2004 obtained from the
Military Health System (MHS) Management Analysis and Reporting Tool.
Progress: This protocol was reported completed in August 2006. A chart review was conducted of
all 182 colonoscopies performed by a FP at an ACH from September 2003 to May 2005. The total
facility cost was $52,632.34 ($289.19 per colonoscopy). The total referral cost would have been
$156,197.60 ($858.23 per colonoscopy). Utilizing a family physician saved the hospital $103,565.26
($569.04 per colonoscopy. A family physician trained in colonoscopy saved significant healthcare
dollars at an Army community hospital by decreasing civilian gastroenterology referrals. Note: the
original title was 'Military Health System Cost Savings by Implementing Colonoscopy Training in
Family Medicine Residency Programs.'
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Detail Summary Sheet
Date: 30 Sep 06 Number: 205131 Status: Completed
Title: Esophagogastroduodenoscopy by a Family Physician: A Case Series Demonstrating
Healthcare Savings
Principal Investigator: MAJ Matthew W. Short, MC
Department: Family Medicine Facility: MAMC
Associate Investigator(s): CPT Lloyd A. Runser, MC
Start - Completion: Funding: Periodic Review:
9/1/2005 - Nov 2005 DCI 8/22/2006
Study Objective: To illustrate the potential cost savings to the military health care system by
implementing esophagogastroduodenoscopy (EGD) training in family medicine residency
programs.
Technical Approach: A cost comparison/analysis will be done to show significant savings to the
TRICARE system by implementing diagnostic upper gastrointestinal endoscopy training in family
medicine residency programs. Procedure reports will be reviewed on all 95 TRICARE beneficiaries
receiving an EGD at Bayne-Jones Army Community Hospital, Fort Polk, LA performed by a
credentialed family physician between Sept 2003 and May 2005. Each procedure will be properly
coded using the standard CPT code for the procedure, anesthesia, and pathology specimens.
Standard E&M codes used by civilian gastroenterologists in the Louisiana community will also be
included to determine the total cost. All reimbursable codes for each patient will then be
multiplied by the actual cost billed to TRICARE in 2004 for the given procedures and outpatient
visits. Data will show the total cost savings to the military health care system by utilizing a single
family physician to perform upper gastrointestinal endoscopies one half day a week at Army
community hospitals. Potential nation-wide yearly cost savings to TRICARE for civilian
gastroenterology EGD referrals will then be determined using the average EGD cost and total
number of civilian referrals in 2004 obtained from the Military Health System (MHS)
Management Analysis and Reporting Tool.
Progress: This protocol was reported completed in August 2006. A chart review was conducted of
all 95 EGDs performed by a FP at an ACH from September 2003 to May 2005. The total facility
cost was $22,655.65 ($238.48 per EGD). The total referral cost would have been $55,614.95
($585.42 per EGD). Utilizing a family physician saved the hospital $32,959.30 ($346.94 per EGD).
An endoscopy-trained family physician saved significant healthcare dollars at an Army community
hospital by decreasing civilian gastroenterology referrals.
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Detail Summary Sheet
Date: 30 Sep 06 Number: 206080
Status: Ongoing
Title: Predicting Intern Performance using an Objective Structured Clinical Examination
Principal Investigator: MAJ Matthew W. Short, MC
Department: Family Medicine
Facility: MAMC
Associate Investigator(s): MAJ Robert B. Blankenship, MC;
COL Bernard J. Roth, MC
MAJ Jennifer E. Jorgensen, MC;
Start - Completion: Funding:
4/18/2006 - Aug 2007 DCI
Periodic Review:
N/A
Study Objective: To determine if intern performance on an Objective Structured Clinical
Examination (OSCE) prior to internship is more predictive than prior academic performance in
identifying potential deficiencies in Accreditation Council for Graduate Medical Education
(ACGME) core competencies during the intern year.
Technical Approach: Sixty-one incoming clinical interns at Madigan Army Medical Center will
complete an Objective Structured Clinical Examination (OSCE) during their intern orientation.
This OSCE will evaluate each intern based on the Accreditation Council for Graduate Medical
Education (ACGME) core competencies of patient care, medical knowledge, practice-based learning
and improvement, interpersonal and communication skills, professionalism, and system-based
practice. The objective of this study is to determine if intern performance on an OSCE prior to
internship is more predictive than prior academic performance based on data from their First Year
Graduate Medical Education (FYGME) application in identifying potential deficiencies in ACGME
core competencies during the intern year. If the OSCE is more predictive of internship
performance, deficiencies in ACGME core competencies identified during this examination could
be remedied earlier to ensure successful completion of internship and result in more competent,
caring physicians.
Progress: This is an educational protocol unrelated to patient care. A total of 61 new interns took
the incoming Objective Structured Clinical Examination (OSCE), evaluating the six ACGME core
competencies. All data from this initial exam has been compiled on a spreadsheet to be analyzed.
Program directors' prediction of performance was also obtained prior to the exam and another
progress report on the intern's performance will be obtained in January. The OSCE will be
repeated at the end of the year, 5/6 June 2207, and the program directors' final evaluations of
intern performance will be collected at that time.
105
Detail Summary Sheets
Graduate Medical Education
106
Detail Summary Sheet
Date: 30 Sep 06 Number: 205090 Status: Ongoing
Title: Attitudes and Perceptions of Refractive Surgery Among ROTC Cadets Presenting for a
Flight Physical and Self-Reported Barriers Towards Having Refractive Surgery to Correct Visual
Acuity and Becoming Medically Qualified for Army Aviation
Principal Investigator: CPT John H. Boden, MC
Department: GME Facility: MAMC
Associate Investigator(s): MAJ John A. Edwards, MC; ETC Mark L. Nelson, MC
Start - Completion: Funding: Periodic Review:
6/2/2005 - Jun 2006 DCI 5/22/2006
Study Objective: To identify attitudes and perceptions ROTC cadets applying for Army aviation
have towards refractive surgery. This protocol will also attempt to identify any perceived barriers
to receiving an exception to policy after having refractive surgery.
Technical Approach: This study will identify attitudes, and perceptions ROTC cadets have
towards refractive surgery, in addition to identifying any perceived barriers cadets might have
towards receiving an exception to policy after having refractive surgery. The study will include
ROTC cadets who will undergo a flight physical medical examination in the year 2005. The sample
population size will be approximately 600 ROTC cadets. Cadets will answer simple questions on a
questionnaire given to them prior to having their flight physical. Analysis of answers provided on
questionnaires will include correlation between subjects understanding of Army policy on
refractive surgery, level of interest in becoming branch aviators, and understanding of the process
entailed in receiving an exception to policy after having refractive surgery.
Progress: This protocol remains ongoing. A total of approximately 640 cadets applying for flight
status during warrior forge 2005 completed the study questionnaire. Data from the questionnaires
has been tabulated and data analysis is currently being worked on.
107
Detail Summary Sheets
Health Outcomes Management Division
108
Detail Summary Sheet
Date: 30 Sep 06 Number: 205108 Status: Ongoing
Title: The Deployment of Physical Therapy for Combat: A Description of the Process and
Outcomes
Principal Investigator: John G. Meyer, MD
Department: Outcomes Facility: MAMC
Associate Investigator(s): LTC Mona 0. Bingham, AN; MAJ Daniel M. Jayne, MC; CPT Brian
W. Jovag, MC
Start - Completion: Funding: Periodic Review:
7/21/2005 - May 2006 DCI 6/29/2006
Study Objective: The overall goal of this study is to describe injuries and the impact of providing
physical therapy evaluation and treatment intervention prior to and during combat deployment for
a brigade (BDE) of soldiers. There are 5 specific aims to meet this overall goal. Using data already
collected from computerized medical records and hospital information systems, the aims of this
secondary data analysis study are: (1) Describe a BDE of soldiers anticipating immediate
deployment and specifically those with physical orthopedic complaints and injuries. (2) Describe
the impact of pre-deploying screening and intervention for orthopedic complaints in a deploying
BDE. (3) Compare orthopedic health and injuries of soldiers in an AD BDE versus soldiers in an
Army National Guard (ARNG) BDE. (4) Describe the impact of physical therapy care provided in
the field environment for a combat BDE during a combat deployment. (5) Compare pre-deployment
Health Risk Assessment II (HRA II) results to post-deployment HRA II results.
Technical Approach: For this retrospective study, data will be obtained from the computerized
medical records available at Madigan Army Medical Center (MAMC) and other health information
system collected as part of the SRP. The population of soldiers assigned to the 81st BDE and the
3rd BDE (and additional units who provided support or were supported by the BDEs during this
deployment) who completed the Soldier Readiness Process (SRP) prior to deployment, immediately
post deployment, and 90-days post deployment will be examined to meet the study goals. This
number is anticipated to be no more than 75% of the BDEs. However descriptive data from the
SRP process on the Health Risk Appraisal II (HRA II) of both BDEs will be collected to adequately
describe the differences and similarities between the 2 BDEs. Data will be collected on a number of
outcome variables including: demographic data, and number of solders in BDE who self-reported
pain, made PT self-referrals, SRP PT referrals, returned via Medical evacuation, seen for
healthcare in theater by PT and other PCP. Other outcome variables include: lost work time,
medical convoy hours, number of PT treatment procedures, number of injuries, type of
injury/diagnosis, time soldier not able to perform combat mission, number of follow-up physical
therapy visits, profile type and length, pain level as determined by physical therapist, final
disposition, and HRA II limited activity answers.
The analysis plan includes a number of different analysis techniques to answer the research
questions/objectives. SPSS will be used to run all descriptive statistics (means, standard
deviations, percentages). To compare orthopedic health and injuries of soldiers in an AD BDE
versus soldiers in an Army National Guard BDE], Chi-square will be used for categorical variables
and either T-tests or Mann- Whitney U tests for measured variables to determine relationships.
ANOVA will be used to determine relationships for interval data. To compare pre-deployment
Health Risk Assessment II (HRA II) results to post-deployment HRA II results], Chi-square will be
used for categorical variables and either T-tests or Mann-Whitney U tests for measured variables
to determine relationships. ANOVA Repeated Measures will be used to determine relationships for
interval data with multiple time points (multiple medical visits/injuries) and Cochran Q.
109
Progress: Initiation of this protocol was significantly delayed due to PCS moves of two study
investigators. This study will resume data analysis during FY07.
110
Detail Summary Sheets
Cardiology Service, Department of Medicine
111
Detail Summary Sheet
Date: 30 Sep 06 Number: 202300 Status: Ongoing
Title: CardioSEAL Septal Occlusion System (HUD)
Principal Investigator: COL David T. Schachter, MC
Department: Medicine/Cardiology Facility: MAMC
Associate Investigator(s): None.
Start - Completion: Funding: Periodic Review:
3/11/2002 - Dec 2004 Nitinol Med Tech via HDE 1/24/2006
Study Objective: Humanitarian Use Device
Technical Approach: The CardioSEAL Septal Occlusion System is approved as an HUD for the
indication of patent foramen oval closure (PFO). MAMC investigators trained to deploy this device
must submit certificates of training and updated curriculum vitae to the Chairman, IRB. Use of
the device will be tracked per 21 CFR 814.124(a).
Progress: Nine patients have undergone successful implantation of the CardioSEAL device
without complications, one during FY06. All patients had strokes/TIA and evidence of PFO by
bubble study. No further stroke/TIA events have been detected in any of the nine patients.
112
Detail Summary Sheet
Date: 30 Sep 06 Number: 201300 Status: Ongoing
Title: Jostent Coronary Stent Graft (HUD)
Principal Investigator: COL David T. Schachter, MC
Department: Medicine/Cardiology Facility: MAMC
Associate Investigator(s): MAJ Bruce R. Kenwood, MC
Start - Completion: Funding: Periodic Review:
9/25/2001 - Sep 2010 Jomed via HDE 8/28/2006
Study Objective: Humanitarian Use Device
Technical Approach: The Jostent Coronary Stent Graft is approved as an HUD for the
indication of arterial perforation. Physicians trained to deploy the stent will be added as associate
investigators upon receipt of documentation of training. Use of the device will be tracked per 21
CFR 814.124(a).
Progress: This Humanitarian Use Device was not utilized during FY06. A Jostent device was
inserted in a patient for a perforated saphenous vein graft in April 2005. The patient is doing well
and continues to be followed.
113
Detail Summary Sheets
Hematology/Oncology Service, Department
of Medicine
114
Detail Summary Sheet
Date: 30 Sep 06 Number: 206113 Status: Ongoing
Title: CTSU E5202: A Randomized Phase III Study Comparing 5-FU, Leucovorin and
Oxaliplatin versus 5-FU, Leucovorin, Oxaliplatin and Bevacizumab in Patients with Stage II
Colon Cancer at High Risk for Recurrence to Determine Prospectively the Prognostic Value of
Molecular Markers
Principal Investigator: LTC Tommy A. Brown, MC
Department: Medicine/Hematology & Oncology Facility: MAMC
Associate Investigator(s): MAJ Angela G. Mysliwiec, MC; MAJ Jasmine T. Daniels, MC; LTC
David E. McCune, MC
Start - Completion: Funding: Periodic Review:
11/28/2006 - Aug 2011 SWOG via Henry M. Jackson Foundation N/A
Study Objective: The primary objective of this study is to demonstrate an improvement in 3-year
disease-free survival for high risk stage II colon cancer patients randomly assigned to 5-FU,
leucovorin, and oxaliplatin (FOLFOX) versus FOLFOX plus bevacizumab.
Secondary objectives of this study are to: Compare overall survival between regimens; further
identify the toxicities of the regimens; prospectively determine the impact of tumor biological
characteristics on the survival of patients with stage II colon cancer.
Technical Approach: In this study, patients determined to be high-risk by the molecular
analysis will receive chemotherapy +/- bevacizumab. A total of 3610 patients will be enrolled in
this study, with up to 10 patients per year enrolled at MAMC. Baseline assessment will include
history and physical, vitals and performance status, CBC, Chemistry, LFTs, CEA, PT, PTT, INR,
urine protein/creatinine (UPC) ratio, and serum pregnancy test if applicable. All eligible,
consenting participants will have a block of resected tumor sent to a central lab for biology-based
risk assessment. Patients found to be low risk, will be registered to Arm C, the observation arm.
Patients found to be high risk, will be randomized to receive either: ARM A (control arm): 5-FU,
leucovorin, and oxaliplatin (FOLFOX regimen) IV every 2 weeks x 12 or ARM B: FOLFOX plus
bevacizumab IV every 2 weeks x 12, followed by bevacizumab alone for 12 additional treatments
(IV every 2 weeks). Patients will be followed every 3 months for 2 years, every 6 months for Year 3
through Year 5, and then every 12 months thereafter for a total of 10 years. Follow-up will include
physical exam, performance status, CEA, and colonoscopy and biopsy where indicated.
Progress: This greater than minimal risk protocol received initial approval with stipulations
during the convened IRB meeting on 25 July 2006. PI response to CIRO review remains pending
at the time of this report.
115
Detail Summary Sheet
Date: 30 Sep 06 Number: 206023 Status: Ongoing
Title: A Multi-Center, Randomized, Phase 3 Study of Iodine 1-131 Tositumomab Therapeutic
Regimen Versus Ibritumomab Tiuxetan Therapeutic Regimen for Subjects with Relapsed or
Transformed Follicular Non-Hodgkin's Lymphoma
Principal Investigator: MAJ Jasmine T. Daniels, MC
Department: Medicine/Hematology & Oncology
Facility: MAMC
Associate Investigator(s): MAJ Angela G. Mysliwiec, MC; LTC David E. McCune, MC; LTC
Antonio G. Balingit, MC; Jane E. Besich-Carter, BS, BCNP
Start - Completion: Funding:
4/13/2006 - Jan 2011 GlaxoSmithKline via Henry M. Jackson
Foundation
Periodic Review:
N/A
Study Objective: This study will compare the proportion of subjects treated with Iodine I 131
tositumomab therapeutic regimen who experience any Grade 3/4 hematological adverse event with
the proportion of subjects treated with ibritumomab tiuxetan therapeutic regimen who experience
this type of adverse event. Subjects in this study must have had at least three prior therapies for
either follicular non-Hodgkin's Lymphoma (NHL) or follicular NHL that has transformed to
diffuse large cell lymphoma.
The secondary objectives for efficacy are comparison of the confirmed overall response rate,
confirmed complete response rate, and duration of response, as well as event-free survival,
progression free survival, time to next treatment, and overall survival between the two treatment
groups. Establishment of the non-inferiority of Iodine I 131 tositumomab compared to
ibritumomab tiuxetan based on event-free survival will be the principal secondary objective.
The secondary safety objectives are safety comparisons between the Iodine I 131 tositumomab and
ibritumomab tiuxetan treatment groups for the following events: Infusional toxicities (all and
Grade 3/4), Gastrointestinal toxicities (all and Grade 3/4), Immune response (Human Anti-Murine
Antibody [HAMA]), Elevated thyroid- stimulating hormone (TSH), Myelodysplastic syndrome
(MDS)/acute myelogenous leukemia (AML), Serious adverse events (SAEs) related to cytopenia
(bleeding events, neutropenic, fever, infections, hospitalization for hematologic supportive care). To
characterize the safety profile in the two treatment groups, including the frequency of adverse
events, the duration of infusion, and tolerance of first subsequent NHL therapy. To summarize
safety and efficacy outcomes during the first subsequent treatment encounter for NHL. To
establish the non-inferiority of confirmed overall response rates and confirmed complete response
rates between Iodine I 131 tositumomab and ibritumomab tiuxetan.
Technical Approach: This is a randomized, multi-center, Phase III study comparing 1131
tositumomab (Bexxar) versus Y90 ibritumomab tiuxetan (Zevalin) in subjects with relapsed or
transformed follicular non-Hodgkin's lymphoma who have received prior treatment with rituximab
(Rituxan). A total of 350 subjects will be randomized into two treatment arms, with up to 10
subjects being enrolled at MAMC. Subjects will be randomly assigned to one of the two treatment
arms. Randomization will be stratified by baseline bone marrow involvement, baseline blood count
and prior fludarabine treatment and conducted separately within each stratum. Subjects on Arm A
will be treated with the standard Zevalin regimen, including rituximab and radiolabeled
ibritumomab tiuxetan in two separate doses for imaging and therapy. Subjects randomized to Arm
B will be treated with the standard Bexxar regimen in two separate doses for imaging and
therapy. Subjects in each arm will be followed for ten years after receiving study drug (five years
for efficacy endpoints and ten years for safety endpoints). After study drug administration, labs
will be drawn at least weekly for up to 13 weeks to closely monitor hematological toxicity.
116
Response assessments will be done at Weeks 7, 13, 26, 39 and 52 during the first year, every six
months during the second year, then annually through five years or until first subsequent
treatment. See schema, protocol page 22. The study is powered to detect a significant reduction of
15% in Grade 3/4 hematologic toxicity. In addition, the study will have 90% power to establish
non-inferiority of the Bexxar treatment versus Zevalin.
Progress: This protocol remains open to patient entry, with no subjects screened or enrolled
during FY06.
117
Detail Summary Sheet
Date: 30 Sep 06 Number: 205094
Status: Terminated
Title: A Randomized, Open-Label Trial Comparing Two Avastin™ (Bevacizumab)-Based
Treatment Regimens For The First-Line Treatment Of Metastatic Colorectal Cancer
Principal Investigator: MAJ Jasmine T. Daniels, MC
Department: Medicine/Hematology & Oncology
Facility: MAMC
Associate Investigator(s): MAJ Angela G. Mysliwiec, MC; LTC David E. McCune, MC
Start - Completion: Funding:
12/15/2005 - Aug 2010 Genentech via Henry M. Jackson Foundation
Periodic Review:
6/28/2006
Study Objective: To compare the efficacy, as measured by progression-free survival (PFS), of
FOLFOX/Avastin followed by FOLFIRI/Avastin versus FOLFAX/Avastin followed by 5-
FU/LV/Avastin as first-line therapy for previously untreated metastatic colorectal cancer.
Secondary Objectives: (1) to evaluate the efficacy, as measured by overall survival, of
FOLFOX/Avastin followed by FOLFIRI/Avastin versus FOLFOX/Avastin followed by 5-
FU/LV/Avastin as first-line therapy for previously untreated metastatic colorectal cancer (2) to
evaluate the tolerability of sequential treatment in subjects during first-line therapy, as measured
by time to first-line treatment response (3) to evaluate the safety of an Irinotecan/Avastin-based
regimen versus 5-FU/Avastin regimen following abbreviated FOLOFOX/Avastin as first-line
therapy for previously untreated metastatic colorectal cancer, as measured by the incidence of
serious adverse events, selected adverse events, and treatment discontinuation for reasons other
than tumor progression.
Technical Approach: This is a randomized, open-label trial comparing two Avastin
(bevacizumab) based treatment regimens for the first-line treatment of metastatic colorectal
cancer. Subjects who qualify will be randomized to one of two treatment arms. Subjects in both
treatment arms will receive FLOFAX/Avastin every 2 weeks for eight cycles. At the end of the first
eight cycles, subjects who have not experienced disease progression will receive treatment as
follows: Arm A subjects will receive FLOFAX/Avastin every 2 weeks until disease progression or
unacceptable toxicity, at which point they will be discontinued from the study. Arm B subjects will
receive 5-FU/LV/Avastin every 2 weeks until disease progression or unacceptable toxicity, at which
point they will be discontinued from the study. All subjects who have documented disease
progression will be discontinued from the study. Subjects will be followed for adverse events for 30
days after the last dose of study treatment or subject discontinuation. Subjects will be followed for
survival and post-progression therapy every 3 months until death, withdrawal of consent, or
termination of the study by Genentech.
Post-progression therapy will not be specified by protocol. It is recommended that as initial post¬
progression therapy, subjects in Arm A receive FOLFOX re-induction if feasible and that subjects
in Arm B receive Irinotecan-based therapy. In conjunction with post-progression therapy, subjects
can receive biological therapy with Avastin and/or Cetuximab at the physician's discretion.
Subjects will be monitored during the entire treatment phase and will be followed as appropriate.
Subjects who are discontinued from treatment for any reason will be evaluated 30 days after the
decision to discontinue study treatment.
Progress: This protocol was terminated by the Study Sponsor due to slower than expected accrual
and an unexpected high rate of early discontinuation from study treatment for reasons not related
to toxicity. No MAMC subjects were screened, consented or enrolled. There are no unreported IND
safety reports at this time.
118
Detail Summary Sheet
Date: 30 Sep 06 Number: 206103 Status: Terminated
Title: Phase 3, Multicenter, Multi-National, Open-Label Study to Evaluate the Safety and
Efficacy of Alfimeprase in Subjects with Occluded Central Venous Access Devices
Principal Investigator: MAJ Jasmine T. Daniels, MC
Department: Medicine/Hematology & Oncology Facility: MAMC
Associate Investigator(s): MAJ Angela G. Mysliwiec, MC; LTC David E. McCune, MC
Start - Completion: Funding: Periodic Review:
Never approved Nuvelo, Inc. via Henry M. Jackson Foundation N/A
Study Objective: To evaluate the safety profile of alfimeprase assessed by monitoring of adverse
events and major bleeding events for up to 120 minutes following the final instillation of
alfimeprase. To evaluate the efficacy of alfimeprase measured by the proportion of subjects with
re-establishment of a functional CVAD at 15 minutes following the initial instillation of study
drug, 30 minutes following the initial instillation of study drug and 30 minutes following the
instillation of one or two doses of study drug.
Technical Approach: This a Phase 3, multicenter, multinational, open label trial to assess the
safety and efficacy of intra-luminal alfimeprase 3.0 mg in subjects with occluded central venous
assess devices (CVAD). A total of 800 subjects will be enrolled and up to 20 at MAMC. Patients
with single lumen, multilumen, centrally inserted, peripherally inserted and implanted ports that
are occluded will be enrolled. They will receive intra-luminal alfimeprase (2ml) and it will be left
in the catheter for up to 30 minutes. Re-establishment of catheter function will be assessed by an
attempt to draw 3mL of blood and infuse 5mL saline at 5, 10, 15, and 30 minutes of first dose. If
patentcy of the catheter is not restored after 30 minutes of first dose of the drug then a second dose
will be administered and left in the catheter for an additional 30 minutes. Safety will be assessed
by monitoring serious adverse events, adverse events and major bleeding events for up to 120
minutes after instillation of the final dose of the drug. Vital signs, venous blood for laboratory
testing will be collected at 8 to 24 hours after instillation of the first study drug dose. After the
study period which could be up to an hour the patients will be followed-up at 2 hours after
instillation of the final study drug dose. Again at 8-24 hours and 28-45 days after instillation of the
first study drug dose. The proportion of patients with re-establishment of functional CVAD at 15
minutes following the instillation of the study drug will be the major efficacy end point.
Progress: This protocol was terminated 27 September 2006, prior to final approval due to failed
contract negotiations with the study sponsor. The study was never initiated at MAMC.
119
Detail Summary Sheet
Date: 30 Sep 06 Number: 205007 Status: Suspended
Title: PSOC 2003: A Phase II Study Evaluating the Efficacy of Gemcitabine, Carboplatin,
Dexamethasone and Rituximab for Previously Treated Lymphoid Malignancies, UW Protocol
Number LYM. 03. 01-
Principal Investigator: MAJ Jasmine T. Daniels, MC
Department: Medicine/Hematology & Oncology
Facility: MAMC
Associate Investigator(s): MAJ Angela G. Mysliwiec, MC; LTC David E. McCune, MC
Start - Completion: Funding:
2/18/2005 - Oct 2009 NCI via Henry M. Jackson Foundation
Periodic Review:
10/24/2006
Study Objective: (1) To determine the feasibility and safety of
Gemcitabine/Carboplatin/Dexamethasone with or without Rituximab in previously treated
lymphoid malignancies. The primary end-point will be response rate (Rituximab will only be
evaluated in CD20 positive malignancies). (2) To determine the efficacy of the above regimen. (3)
To determine the ability to proceed to blood stem peripheral blood collection following the above
regimens the impact of above regimen on stem cell reserve. (4) To determine remission duration.
Technical Approach: PSOC 2003 is a multicenter single arm phase II trial of Gemcitabine,
Carboplatin, and Dexamethasone in the treatment of recurrent or refractory lymphoma (including
B-cell, T-cell, and Hodgkin's disease). Patients with C020 positive B-cell lymphoma will also be
treated with Rituximab. The end points of the trial include response rate, duration of remission,
and the ability to collect stem cells for possible future autologas stem cell transplant. The goal
accrual of the study is 51 patients over 2 to 3 years. We anticipate accruing two patients per year
at Madigan. The study will be monitored for accrual, adverse events and patient deaths every 6
months by the Study Investigator, Dr Ajay Gopal of the University of Washington and the Fred
Hutchinson Cancer Research Center, and will be monitored annually by the Fred Hutchinson
Cancer Research Center Protocol Data Monitoring Committee.
Progress: This protocol remains open to enrollment with one patient enrolled at MAMC who
continued to be followed during FY06.
120
Detail Summary Sheet
Date: 30 Sep 06 Number: 89080 Status: Terminated
Title: SWOG 8814 (ECOG 4188, NCCTG 883051): Phase III Comparison of Adjuvant
Chemoendocrine Therapy with CAF and Concurrent or Delayed Tamoxifen to Tamoxifen Alone
in Postmenopausal Patients with Breast Cancer Having Involved Axillary Nodes and Positive
Hormone Receptors
Principal Investigator: MAJ Jasmine T. Daniels, MC
Department: Medicine/Hematology & Oncology Facility: MAMC
Associate Investigator(s): MAJ Angela G. Mysliwiec, MC; LTC David E. McCune, MC; LTC
Tommy A. Brown, MC
Start - Completion: Funding: Periodic Review:
10/20/1989 - Indef SWOG via Henry M. Jackson Foundation 8/14/2006
Study Objective: To compare disease-free survival and overall survival of postmenopausal
primary breast cancer patients with involved axillary nodes and positive estrogen and/or
progesterone receptors treated with standard adjuvant therapy with long-term Tamoxifen or with
chemoendocrine therapy with CAF, followed by long-term Tamoxifen or with concurrent
chemoendocrine therapy with Tamoxifen and CAF and to compare the relative toxicity of the three
therapies.
Technical Approach: Tumors must be pathologic stage Tl, T2, or T3; N; MO (Stage II or selected
Stage IIIA). Patients must have histologically proven adenocarcinoma of the breast with at least
one positive lymph node (tumor and/or nodes must not be fixed). Patients must have undergone a
radical, modified radical, or breast sparing procedure plus axillary dissection (level I or level II).
Patients with bilateral breast cancer are ineligible. Estrogen and progesterone receptors must be
assayed and one and/ or the other must be positive by the institutional laboratory standards of >10
fmol/mg protein. Prestudy studies must reveal no evidence of metastatic disease. Prior hormonal
or chemotherapy is not allowed and prior postmenopausal estrogen therapy is allowed but must be
discontinued before registration. Stratification factors will include: involved nodes (1-3, >4); PgR+
(ER positive or negative) vs PgR(ER positive); time from surgery to randomization (<6 vs >6
weeks). Patients will be randomized to one of three treatment arms: Arm I: Tamoxifen x 5 years,
Arm II: Intermittent CAF x 6 courses followed by Tamoxifen x 5 years, Arm III: Intermittent CAF
x 6 courses with concurrent Tamoxifen x 5 years.
Progress: This protocol closed to patient entry in August 1995, with six patients enrolled at
MAMC; three who remained in long-term follow-up. The protocol was terminated during FY06 and
the three surviving patients will continue to be followed under MAMC #99019, SWOG S9808:
Long-Term Follow-Up Protocol: An Administrative Tool.
121
Detail Summary Sheet
Date: 30 Sep 06 Number: 90027 Status: Ongoing
Title: SWOG 8851 (EST 5811, INT-0101): Phase III Comparison of Combination Chemotherapy
(CAF) and Chemohormonal Therapy (CAF + Zoladex or CAF + Zoladex + Tamoxifen) in
Premenopausal Women with Axillary Node-Positive, Receptor- Positive Breast Cancer
Principal Investigator: MAJ Jasmine T. Daniels, MC
Department: Medicine/Hematology & Oncology Facility: MAMC
Associate Investigator(s): MAJ Angela G. Mysliwiec, MC; LTC David E. McCune, MC; LTC
Tommy A. Brown, MC
Start - Completion: Funding: Periodic Review:
2/16/1990 - Indef SWOG via Henry M. Jackson Foundation 12/4/2006
Study Objective: To compare the recurrence rates, disease-free intervals, relative toxicities, and
hormone-receptor-positive survival for premenopausal women with axillary lymph node-positive
breast cancer given adjuvant therapy with combination chemotherapy using cyclophosphamide,
doxorubicin, and 5-FU (CAF) alone or CAF followed by Zoladex, or CAF followed by Zoladex plus
Tamoxifen; and to assess the effect of CAF, CAF plus Zoladex, and CAF plus Zoladex and
Tamoxifen on hormone levels (LH, FSH, and estradiol) in these patients.
Technical Approach: Patients will be nonpregnant females who have undergone excision of the
primary breast tumor mass, proven histologically to be invasive breast adenocarcinoma and must
have one or more pathologically involved axillary nodes. Patients who undergo total mastectomy
may receive post-operative radiotherapy at the discretion of the investigator. Patients who have
had prior hormonal therapy or chemotherapy for breast cancer are ineligible. Patients will be
randomized to CAF alone for six cycles or to CAF for 6 cycles followed by monthly Zoladex for 5
years, or to CAF for 6 cycles followed by daily Tamoxifen and monthly Zoladex for 5 years.
Adjuvant therapy will be instituted as soon as possible after mastectomy or lumpectomy. The
interval between definitive surgery and initiation of adjuvant chemotherapy will not be >12 weeks.
When planned, radiation therapy may be administered prior to or after (within 4 weeks of)
completion of 6 cycles of adjuvant chemotherapy.
Progress: This protocol closed to patient entry in February 1994, with 6 patients enrolled. Three
patients are deceased and three remain disease free and continued to be followed at MAMC during
FY06.
122
Detail Summary Sheet
Date: 30 Sep 06 Number: 90029 Status: Terminated
Title: SWOG 8897 (EST-2188, CALGB-8897, INT-0101): Phase III Comparison of Adjuvant
Chemotherapy With or Without Endocrine Therapy in High-Risk, Node Negative Breast Cancer
Patients, and a Natural History Follow-up Study in Low-Risk, Node Negative Patients
Principal Investigator: MAJ Jasmine T. Daniels, MC
Department: Medicine/Hematology & Oncology Facility: MAMC
Associate Investigator(s): MAJ Angela G. Mysliwiec, MC; LTC David E. McCune, MC; LTC
Tommy A. Brown, MC
Start - Completion: Funding: Periodic Review:
1/19/1990 - Indef SWOG via Henry M. Jackson Foundation 12/1/2005
Study Objective: To compare disease-free survival and overall survival of high risk primary
breast cancer patients with negative axillary lymph nodes treated with standard adjuvant
chemotherapy for 6 cycles; either CMF (cyclophosphamide, methotrexate, 5-FU) or CAF
(cyclophosphamide, adriamycin, 5-FU); to assess the value of the addition of tamoxifen for five
years compared to no tamoxifen in these patients; to compare the toxicity of the therapies; to
assess the prognostic significance of DNA flow cytometry in patients with small, occult invasive
breast cancer treated by local therapy only; and to evaluate the disease-free survival and survival
of low risk invasive breast cancer patients determined by receptor status, tumor size, and % S
phase treated by local therapy only.
Technical Approach: Patients must have undergone a radical, modified radical, or breast
sparing procedure plus level 1 and 2 axillary lymph node dissection. Patients with bilateral breast
cancer, prior hormonal or chemotherapy, or previous or concurrent malignancy are ineligible. Low
risk patients will be followed but will not receive adjuvant therapy. High risk patients will be
randomized to: (1) CMF x 6 cycles; (2) CAF x 6 cycles; (3) CMF x 6 cycles followed by tamoxifen; or
(4) CAF x 6 cycles followed by tamoxifen. Patients will start adjuvant chemotherapy within 12
weeks of definitive surgery. Patients who have had a breast sparing procedure and axillary
dissection will receive radiation therapy, either before or after CMF or CAF (at the discretion of
the treating physician). Radiotherapy and tamoxifen may be given together. Patients will be
removed from the study for unacceptable toxicity, development of local/regional or metastatic
disease; or noncancer related illnesses that prevent continuation of therapy or regular follow-up.
Patients will be followed until death.
Progress: This protocol closed to patient entry in January 1993, with six patients enrolled at
MAMC who remain disease free. The protocol was terminated during FY06 and the six surviving
patients will continue to be followed under MAMC #99019, SWOG S9808: Long-Term Follow-Up
Protocol: An Administrative Tool.
123
Detail Summary Sheet
Date: 30 Sep 06 Number: 90056 Status: Completed
Title: SWOG 8997 (ECOG 3887): Phase III Chemotherapy of Disseminated Advanced Stage
Testicular Cancer with Cisplatin Plus Etoposide with Either Bleomycin or Ifosfamide
Principal Investigator: MAJ Jasmine T. Daniels, MC
Department: Medicine/Hematology & Oncology Facility: MAMC
Associate Investigator(s): MAJ Angela G. Mysliwiec, MC; LTC David E. McCune, MC; LTC
Tommy A. Brown, MC
Start - Completion: Funding: Periodic Review:
4/20/1990 - Indef SWOG via Henry M. Jackson Foundation 2/8/2006
Study Objective: To determine the objective response rate and duration of remission of BEP
compared to VIP combination chemotherapy; to determine the toxicity of VIP compared to BEP
combination chemotherapy; to confirm the efficacy and toxicity of intravenous Mesna as a
urothelial protective agent.
Technical Approach: Patients must have a histologic diagnosis of advanced disseminated germ
cell tumor and no prior chemotherapy or radiation therapy. Patients will be randomized to VIP
(cisplatin, ifosfamide, mesna, and etoposide) to BEP (cisplatin, etoposide, and bleomycin). The
regimen will be repeated every three weeks for four cycles. Bleomycin will be omitted for
postsurgery chemotherapy in BEP patients. Patients in complete remission at the end of four
courses of therapy will receive no further treatment. If there is radiographic or serologic evidence
of persistent disease and residual tumor is surgically resectable, surgery will be performed.
Patients who have complete or near complete resection of residual radiographic abnormalities with
the pathologic finding of fibrosis/necrosis and those who have complete resection of mature or
immature teratoma will receive no further treatment. Patients who have complete resection of
residual disease which histologically shows viable carcinoma will receive two more courses of the
original induction therapy. If residual tumor is deemed unresectable, patients will be followed
monthly until disease progression with no further therapy. If relapse occurs in complete or partial
responders less than 4 weeks after day 1 of the last course of induction therapy, the patient will be
taken off study.
Progress: This protocol closed to patient entry in April 1992, with one patient enrolled. The
protocol was reported completed during FY06 when long-term follow-up data was no longer
required on the surviving patient.
124
Detail Summary Sheet
Date: 30 Sep 06 Number: 97096 Status: Ongoing
Title: SWOG 9059 (E1392, INT-0126): Phase III Comparison of Standard Radiotherapy versus
Radiotherapy plus Simultaneous Cisplatin, versus, split-Course Radiotherapy plus
Simultaneous Cisplatin and 5-Fluorouracil, in Patients with Unresectable Squamous Cell
Carcinoma of the Head and Neck
Principal Investigator: MAJ Jasmine T. Daniels, MC
Department: Medicine/Hematology & Oncology Facility: MAMC
Associate Investigator(s): MAJ Angela G. Mysliwiec, MC; LTC David E. McCune, MC; LTC
Tommy A. Brown, MC
Start - Completion: Funding: Periodic Review:
5/16/1997 - Indef SWOG via Henry M. Jackson Foundation 4/10/2006
Study Objective: 1) To compare the effectiveness of standard radiation therapy alone to radiation
therapy and simultaneous chemotherapy with cisplatin to split-course radiation therapy with
cisplatin and 5-fluorouracil infusion in patients with unresectable Stage III and IV squamous cell
carcinoma of the head and neck. Endpoints will include complete response rate, time to treatment
failure, and overall survival. 2) To compare the relative toxicities of these treatment arms, in this
patient population. 3) To compare patterns of relapse or treatment failure among these regimens.
4) To further assess the role, timing, and success of surgery in patients achieving a response to
non-operative therapy.
Technical Approach: Unresectable Squamous Cell Carcinoma has a dismal prognosis with 3
year survivals in the 25' range. Several studies have shown that adding chemotherapy to radiation
therapy may improve response rates and may allow some patients to get surgery after therapy.
There are two approaches to adding chemotherapy to radiation therapy. One way is to give
concurrent therapy with Cisplatinum alone with combined continuous radiation therapy (A1 Sarraf
regimen) or to give combination Cisplatinum and 5-FU with split course (Adelstein Regimen).
These two regimens have met with some success in single ARM Phase II studies and have resulted
in some patients having subsequent surgeries translating into longer survivals. It is thus the aim
of this study to evaluate efficacy of three different regimens with continuous radiation therapy
alone serving as the third ARM. Toxicities from these regimens are reasonable.
Progress: This protocol closed to patient entry in April 2000, with two patients enrolled. One
patient died of progressive disease and the other patient remains disease free and continued to be
followed at MAMC during FY06.
125
Detail Summary Sheet
Date: 30 Sep 06 Number: 93032 Status: Ongoing
Title: SWOG 9061 (EST-2190, INT 0121): A Phase III Study of Conventional Adjuvant
Chemotherapy vs High Dose Chemotherapy and Autologous Bone Marrow Transplantation or
Stem Cell Transplantation as Adjuvant Intensification Therapy Following Conventional
Adjuvant Chemotherapy in Patients with Stage II and III Breast Cancer at High Risk of
Recurrence
Principal Investigator: MAJ Jasmine T. Daniels, MC
Department: Medicine/Hematology & Oncology Facility: MAMC
Associate Investigator(s): MAJ Angela G. Mysliwiec, MC; LTC David E. McCune, MC; LTC
Tommy A. Brown, MC
Start - Completion: Funding: Periodic Review:
10/7/1993 - Indef SWOG via Henry M. Jackson Foundation 10/31/2006
Study Objective: To compare the sites and rates of recurrence, disease-free survival and overall
survival, and toxicity of adjuvant chemotherapy (CAF) with adjuvant chemotherapy plus high-dose
therapy with cyclophosphamide and the TEPA with autologous marrow infusion in patients with
breast cancer with 10 or more positive lymph nodes.
Technical Approach: Patients will be stratified according to estrogen receptor status, age, and
menopausal status and then randomized to receive radiotherapy plus tamoxifen or high-dose
chemotherapy and autologous bone marrow transplantation. Both arms will receive
cyclophosphamide 100 mg/m2 PO X 14 days, doxorubuicin 30 mg/m2 IV days 1 & 8, and flurouracil
500 mg/m2 IV days 1 & 8 repeated every 28 days x 6 cycles (CAF). Patients receiving CAF without
bone marrow transplantation will begin radiation therapy within 4 weeks of the last dose of
chemotherapy or when the WBC > 2900 and Platelets > 100,000. Patients randomized to receive
high-dose chemotherapy will have bone marrow harvested no sooner than 4 weeks nor longer than
8 weeks after the last previous dose of myelotoxic chemotherapy. The CBC must be normal and the
bone marrow normocellular and free of tumor by bilateral iliac crest biopsy within 4 weeks prior to
storage. After the bone marrow is harvested, high-dose chemotherapy of cyclophosphamide 6000
mg/m2/96 hr and ThioTEPA 800 mg/m2/96 hr (4 days), will be given by continuous infusion over 4
days, days -6 to -2. Autologous bone marrow reinfusion will be on day 0. Patients receiving BMT
will again be randomized to receive GM-CSF as a daily 2, 6 or 24 hour intravenous infusion
beginning 2-4 hours after bone marrow infusion. GM-CSF will be initiated at a dose of 250
mcg/m2/d. Treatment will continue until the patient has achieved an absolute neutrophil count
(ANC) of = 1000 cells/ul on 3 consecutive days or a planned duration of 28 days of treatment.
Tamoxifen 20 mg PO q.d. will be given to all patients who are estrogen or progesterone
receptor positive after the completion of all chemotherapy for 5 years. For patients not randomized
to receive transplant, Tamoxifen should be initiated 28 days after the start of the last CAF cycle.
Patients randomized to receive transplant should begin Tamoxifen following transplant when
WBC > 4000 and/or ANC > 2000. Patients will be taken off-study if there is development of
metastatic disease at any time while therapy is ongoing. Measurement of effect is recurrence,
disease-free survival or survival (survival is measured from the date of randomization to date of
death). At measured times during the study a Breast Chemotherapy Questionnaire (BCQ) will be
completed to separately document the changes in psychosocial function that occur on the two
regimens. Not all subjects will complete the questionnaire at all time points, but if at least 150 per
arm have complete data, the width of a 95% confidence interval on the mean change in scores
would be about ± 0.09. The BCQ will also be used to make comparisons between regimens. A 2
degree of freedom test based on the difference of the means of the 36 week evaluation and the
difference of the means of the 52 week evaluation will be used.
126
Progress: This protocol closed to patient entry in August 1998, with one patient enrolled who
remains disease free and continued to be followed at MAMC during FY06.
127
Detail Summary Sheet
Date: 30 Sep 06 Number: 93097
Status: Ongoing
Title: SWOG 9205: Central Prostate Cancer Serum Repository Protocol
Principal Investigator: MAJ Jasmine T. Daniels, MC
Department: Medicine/Hematology & Oncology
Facility: MAMC
Associate Investigator(s): MAJ Angela G. Mysliwiec, MC; LTC David E. McCune, MC; LTC
Tommy A. Brown, MC
Start - Completion: Funding:
Periodic Review:
5/7/1993 - Indef SWOG via Henry M. Jackson Foundation
4/10/2006
Study Objective: 1) To store serum of patients with confirmed adenocarcinoma of the prostate
entered onto clinical trials conducted by the SWOG Genitourinary Committee. 2) To provide the
serum of the above patients entered onto SWOG studies for specific clinical-laboratory
investigations outlined on separate SWOG protocols approved by the Genitourinary Committee
Tumor Biology Subcommittee.
Technical Approach: This serum bank is to provide the opportunity for study of new or existing
markers or other tests in a prospective or retrospective fashion, in order to test their usefulness as
diagnostic or management tools in prostate cancer at all stages. Specific information regarding the
nature of individual tests to be conducted on the serum samples of these patients will be described
in individual protocols. All serum samples (approx. 3 - 5 cc) will be collected from patients in the
frequency and timing indicated on specific protocols. Samples will be spun 15 minutes after
collection and stored at a minimum of -20°C. Samples will be frozen and shipped to the Serum
Bank Coordinator.
Progress: This prostate cancer companion protocol remains open to enrollment with 14 patients
enrolled at MAMC, two during FY06.
128
Detail Summary Sheet
Date: 30 Sep 06 Number: 93136 Status: Ongoing
Title: SWOG 9221, MDACC ID 91-025, INT-191-001: Phase III Double-Blind Randomized Trial
of 13-Cis Retinoic Acid (13-cRA) to Prevent Second Primary Tumors (SPTs) in Stage I Non-Small
Cell Lung Cancer
Principal Investigator: MAJ Jasmine T. Daniels, MC
Department: Medicine/Hematology & Oncology Facility: MAMC
Associate Investigator(s): MAJ Angela G. Mysliwiec, MC; LTC David E. McCune, MC; LTC
Tommy A. Brown, MC
Start - Completion: Funding: Periodic Review:
7/2/1993 - Indef SWOG via Henry M. Jackson Foundation 5/24/2006
Study Objective: To evaluate: (1) the efficacy of 13-cis-retinoic acid (13-cRA) in reducing the
incidence of SPTs in patients who have been treated for Stage I non-small cell lung cancer with
complete surgical resection; (2) the qualitative and quantitative toxicity of 13-cRA in a daily
administration schedule; and (3) compare the overall survival of patients treated with 13-cRA vs.
patients treated with placebo.
Technical Approach: Patients enrolling into this study will be stratified according to histology, T
stage and smoking status then registered into a Single-Blind, 8 week run-in period to test
compliance. All patients will receive placebo during this period. After Run-in the patients will be
randomized into a double-blind trial to receive 13-cRA (30 mg p.o./d x 3 yrs vs. Placebo (30 mg
p.o./d x 3 yrs). Each group will have a 4 year follow-up period.
The final analysis will be undertaken shortly after seven years. The primary hypothesis for
the study is whether 13-cRA lowered the rate of second primary tumors (SPT). All patients
randomized will be grouped according to the assigned treatment. Patients who are either purely
lost to follow up or died without a SPT occurring will be included in the actuarial analysis with a
censored status on the last day of contact. The primary hypothesis of treatment benefit will be
tested using the proportional hazards model.
Progress: This protocol closed to patient entry in April 1997, with eight patients enrolled who
remain disease free and continued to be followed at MAMC during FY06.
129
Detail Summary Sheet
Date: 30 Sep 06 Number: 93166 Status: Ongoing
Title: SWOG 9303: Phase III Study of Radiation Therapy, Levamisole, and 5-Fluorouracil versus
5-Fluorouracil and Levamisole in Selected Patients With Completely Resected Colon Cancer
Principal Investigator: MAJ Jasmine T. Daniels, MC
Department: Medicine/Hematology & Oncology Facility: MAMC
Associate Investigator(s): MAJ Angela G. Mysliwiec, MC; LTC David E. McCune, MC; LTC
Tommy A. Brown, MC
Start - Completion: Funding: Periodic Review:
11/5/1993 - Indef SWOG via Henry M. Jackson Foundation 8/14/2006
Study Objective: To determine whether 5-FU, levamisole and radiation therapy results in
superior overall survival when compared to 5-FU and levamisole without radiation therapy in the
management of patients with completely resected pathologic stage T4BN0-2 colon cancer and
selected patients with T3N1-2 colon cancer.
Technical Approach: This randomization clinical trial will compare radiation therapy, 5FU and
levamisole with 5FU and levamisole in patients with completely resected colon cancer at high risk
for local-regional recurrence and limited risk for system disease.
We will compare 5FU and levamisole, as delivered in the prior intergroup study, with one
month of 5FU and levamisole followed by 5-5 1/2 weeks of 5FU, levamisole, and local-regional RT
(45-50.4 Gy in 25-28 fractions), followed by 43 weeks of 5FU and levamisole.
Progress: This protocol closed to patient entry in December 1996, with one patient enrolled
during FY95, who remains disease free and continued to be followed at MAMC during FY06.
130
Detail Summary Sheet
Date: 30 Sep 06 Number: 94170 Status: Terminated
Title: SWOG 9313: Phase III Comparison of Adjuvant Chemotherapy With High-Dose
Cyclophosphamide + Doxorubicin vs Sequential Doxorubicin Followed by Cyclophosphamide in
High-Risk Breast Cancer Patients with 0-3 Positive Nodes
Principal Investigator: MAJ Jasmine T. Daniels, MC
Department: Medicine/Hematology & Oncology Facility: MAMC
Associate Investigator(s): MAJ Angela G. Mysliwiec, MC; LTC David E. McCune, MC; LTC
Tommy A. Brown, MC
Start - Completion: Funding: Periodic Review:
9/21/1994 - Indef SWOG via Henry M. Jackson Foundation 8/14/2006
Study Objective: 1) To compare disease-free survival, overall survival, and toxicity of high-risk
primary breast cancer patients with negative axillary lymph nodes or with one to three positive
nodes treated with adjuvant high-dose chemotherapy with doxorubicin plus cyclophosphamide,
versus high-dose sequential chemotherapy with doxorubicin followed by cyclophosphamide. 2) To
obtain tumor tissue for biologic studies.
Technical Approach: Women with primary breast invasive adenocarcinoma, will be randomized
to one of two treatments: 1) High dose doxorubicin + cyclophosphamide x 6 cycles, or 2) High dose
sequential doxorubicin x 4 cycles, followed by high dose cyclophosphamide x 3. Women who are
postmenopausal and have receptor + will receive Tamoxifen for 5 years.
Progress: This protocol closed to patient entry in May 1997, with one patient enrolled who
remains disease free and continued to be followed at MAMC. The protocol was terminated during
FY06, and the surviving patient will continue to be followed under MAMC #99019, SWOG S9808:
Long-Term Follow-Up Protocol: An Administrative Tool.
131
Detail Summary Sheet
Date: 30 Sep 06 Number: 95003 Status: Ongoing
Title: SWOG 9401: A Controlled Phase III Evaluation of 5-FU Combined with Levamisole and
Leucovorin as Surgical Adjuvant Treatment Following Total Gross Resection of Metastatic
Colorectal Cancer
Principal Investigator: MAJ Jasmine T. Daniels, MC
Department: Medicine/Hematology & Oncology Facility: MAMC
Associate Investigator(s): MAJ Angela G. Mysliwiec, MC; LTC David E. McCune, MC; LTC
Tommy A. Brown, MC
Start - Completion: Funding: Periodic Review:
11/18/1994 - Indef SWOG via Henry M. Jackson Foundation 10/10/2006
Study Objective: To determine in patients who have undergone complete gross surgical resection
of metastatic colorectal cancer whether postoperative adjuvant chemotherapy with a new regimen
of 5-fluorouracil (5-FU) plus leucovorin plus levamisole will result in improved survival compared
to postoperative adjuvant chemotherapy with a standard 5-FU plus levamisole regimen.
Technical Approach: Patients will be randomly selected to treatment Arm I or treatment Arm
II. Arm I consists of the standard regimen of 5-FU given by rapid intravenous infusion for 5
consecutive days, plus levamisole given by mouth three times daily for three consecutive days
every other week for one year. Arm II is a new chemotherapy regimen which adds leucovorin in
addition to the 5-FU and levamisole. 5-FU and leucovorin are given by rapid intravenous injection
for five consecutive days every four to five weeks for one year. Levamisole is given by mouth three
times per day for three days in a row every two weeks during the first two months, then every 2-3
weeks for a total of one year.
Progress: This protocol closed to patient entry in September 1996, with one patient enrolled who
remains disease free and continued to be followed at MAMC during FY06.
132
Detail Summary Sheet
Date: 30 Sep 06 Number: 95093 Status: Ongoing
Title: SWOG 9402: Phase III Intergroup Randomized Comparison of Radiation Alone vs Pre-
Radiation Chemotherapy for Pure and Mixed Anaplastic Oligodendrogliomas
Principal Investigator: MAJ Jasmine T. Daniels, MC
Department: Medicine/Hematology & Oncology Facility: MAMC
Associate Investigator(s): MAJ Angela G. Mysliwiec, MC; LTC David E. McCune, MC; LTC
Tommy A. Brown, MC
Start - Completion: Funding: Periodic Review:
5/19/1995 - Indef SWOG via Henry M. Jackson Foundation 2/8/2006
Study Objective: 1) overall survival 2) compare time to tumor progression between the two arms
3) the frequency of severe (= grade 3) toxicities will be examined. 4) compare quality of life and
neurologic function between the two arms. 5) identify the key histopathologic criteria necessary to
make the diagnosis of anaplastic oligodendroglioma and mix oligo-astrocytoma; evaluate the
diagnostic and prognostic relevance of chromosomal alterations; evaluate the diagnostic and
prognostic relevance of DNA ploidy and indices of proliferation including percent S and percent
G2M; study the diagnostic and prognostic relevance of immunohistochemical markers of cellular
function and/or glial development; and evaluate the transnational relevance of tumor suppressor
genes and oncogenes.
Technical Approach: This is a non-blinded randomized intergroup study and is different from
other randomized trials for malignant glioma in three respects. First, it will evaluate the role of
adjuvant chemotherapy in a recognizible subset of patients with malignant glioma, those with
oligodendroglial differentiation. Second, the RT treatment volume will be based on a postoperative
pre-randomization MR image, rather than the customary preoperative diagnostic CT or MR. Third,
in the experimental arm of this study, chemotherapy will be given prior to RT. Patients whose
tumors progress on chemotherapy will proceed to RT immediately. There will be a central
pathology review prior to randomization, central radiology review to assess response to PCV and to
substantiate tumor progression, and a quality of life assessment (QLA) to document the acute and
chronic toxicities of chemotherapy and radiation including effects on cognitive function. Surgery
and radiotherapy ± PCV may adversely affect a patient's physical and emotional functioning. The
Karnofsky performance status (KPS) will measure physical well-being. To complement KPS, the
Mini-Mental Status exam (MMSE) will be administered to patients to assess cognitive ability.
Assessment of differences in quantitative survival will be performed between the two therapeutic
regimens supplemented with qualitative survival by the assessment of KPS, MMSE, and QLA.
Progress: This protocol closed to patient entry in March 2002, with one patient enrolled who
remains disease free and continued to be followed during FY06.
133
Detail Summary Sheet
Date: 30 Sep 06 Number: 94163 Status: Ongoing
Title: SWOG 9410 (INT 0148): Doxorubicin Dose Escalation, With or Without Taxol, As Part of
the CA Adjuvant Chemotherapy Regimen for Node Positive Breast Cancer: A Phase III
Intergroup Study
Principal Investigator: MAJ Jasmine T. Daniels, MC
Department: Medicine/Hematology & Oncology Facility: MAMC
Associate Investigator(s): MAJ Angela G. Mysliwiec, MC; LTC David E. McCune, MC; LTC
Tommy A. Brown, MC
Start - Completion: Funding: Periodic Review:
1/20/1995 - Indef SWOG via Henry M. Jackson Foundation 8/29/2006
Study Objective: To determine (1) whether dose escalation of doxorubicin used as an adjuvant
with cyclophosphamide in patients with early breast cancer will increase disease free and overall
survival; (2) whether the use of Taxol as a single agent after the completion of 4 cycles of
cyclophosphamide and doxorubicin in combination will further improve disease-free and overall
survival compared to cyclophosphamide and doxorubicin alone; (3) if Taxol following standard dose
cyclophosphamide and doxorubicin will be as effective or more effective than high dose
cyclophosphamide and doxorubicin without Taxol; (4) to access the toxicity of the different doses of
cyclophosphamide and doxorubicin with and without Taxol using the end point of life threatening
or lethal toxicity; (5) whether the longer duration of chemotherapy treatment for patients
randomized to receive Taxol is associated with a reduction in local recurrence in patients with
lumpectomy and radiotherapy.
Technical Approach: Women with breast cancer, who have been treated with either mastectomy
or segmentectomy will receive adjuvant chemotherapy. All patients will receive 4 courses of
cyclophosphamide and doxorubicin (21 day cycle), but the doxorubicin dose will vary depending
upon the randomization. Patients randomized to high dose doxorubicin will also receive G-CSF &
ciprofloxacin. Some women will be randomized to receive Taxol after 4 cycles of AC chemotherapy
is completed. They will receive taxol day 1 of a 21 day cycle for 4 cycles. Women with ER positive
tumors will be given tamoxifen for 5 years.
Progress: This protocol closed to patient entry in April 1997, with nine patients enrolled. Four
patients died due to disease progression and four patients remain disease free and continued to be
followed during FY06.
134
Detail Summary Sheet
Date: 30 Sep 06 Number: 96095 Status: Ongoing
Title: SWOG 9514: Phase III Double-Blind, Placebo-Controlled, Prospective Randomized
Comparison of Adjuvant Therapy with Tamoxifen vs. Tamoxifen & Fenretinide in
Postmenopausal Women with Involved Axillary Lymph Nodes and Positive Receptors,
Intergroup
Principal Investigator: MAJ Jasmine T. Daniels, MC
Department: Medicine/Hematology & Oncology Facility: MAMC
Associate Investigator(s): MAJ Angela G. Mysliwiec, MC; LTC David E. McCune, MC; LTC
Tommy A. Brown, MC
Start - Completion: Funding: Periodic Review:
6/21/1996 - Indef SWOG via Henry M. Jackson Foundation 3/15/2006
Study Objective: 1) To compare disease-free survival and overall survival of postmenopausal
primary breast cancer patients with involved axillary nodes and positive estrogen or progesterone
receptors who are treated with standard adjuvant tamoxifen vs. tamoxifen and fenretinide; 2) to
gain wider experience and toxicity information on the combination of tamoxifen and fenretinide;
and 3) to obtain tumor tissue from these patients for future biologic studies of relevance to this
patient population.
Technical Approach: The present standard of therapy for node positive and ER positive post
menopausal women is Tamoxifen alone. There are some studies that suggest that the addition of
adjuvant chemotherapy combined with hormonal therapy will prolong relapse free and overall
survival. However, not all patients, especially in the over 65 year old age group, can tolerate or
want the significant side effects of chemotherapy. Thus, a less toxic regimen is needed. This study
attempts to use a chemoprophylactic approach along with the standard Tamoxifen treatment for
this group of patients. This new retinoid has shown some effectiveness in Phase I and II studies
when given in combination with Tamoxifen to untreated metastatic breast cancer patients. This
study will test its use in a Phase III randomized, prospective, placebo-controlled trial. The side
effects seem to be fairly minimal except for night blindness which will be closely monitored during
this trial.
Progress: This protocol closed to patient entry in November 1999, with four patients enrolled who
remain disease free and continue to be followed at MAMC during FY06.
135
Detail Summary Sheet
Date: 30 Sep 06 Number: 96118 Status: Ongoing
Title: SWOG 9515: Phase III Intergroup Trial of Surgery Followed by (1) Radiotherapy vs. (2)
Radiochemotherapy for Resectable High Risk Squamous Cell Carcinoma of the Head and Neck
Principal Investigator: MAJ Jasmine T. Daniels, MC
Department: Medicine/Hematology & Oncology Facility: MAMC
Associate Investigator(s): MAJ Angela G. Mysliwiec, MC; LTC David E. McCune, MC; LTC
Tommy A. Brown, MC
Start - Completion: Funding: Periodic Review:
9/20/1996 - Indef SWOG via Henry M. Jackson Foundation 4/10/2006
Study Objective: 1) To determine the efficacy of concurrent cisplatinum and radiotherapy
following surgical resection in patients who have advanced squamous cell carcinoma of the head
and neck region; 2) to test whether the use of concurrent chemoradiotherapy following surgery
increases locoregional control rates; 3) to determine if the patterns of first failure are changed by
the use of concurrent chemotherapy; 4) to determine whether the use of concurrent
chemoradiotherapy prolongs disease-free survival and/or overall survival; and 5) to compare the
toxicity of concurrent chemoradiotherapy versus radiation alone in the postoperative setting.
Technical Approach: In head and neck squamous cell carcinomas with high risk features, there
is a 20 to 50 percent recurrence rate after surgical resection. These high risk features include
greater than 2 lymph nodes positive, extracapsular extension of cancer in lymph nodes, and
positive resection margins. In the past, patients with these high risk features had received
radiation therapy for local control. There is evidence, however, that the addition of cisplatinum
with concurrent radiation therapy may help in local control. This data comes from in vitro as well
as in vivo data showing cisplatinum may be a radiation sensitizer that may have synergistic local
effects on malignancies. The study is a Phase III randomized study that will compare standard
radiation therapy against concurrent cisplatinum and radiation therapy for resected squamous cell
carcinoma of the head and neck. The added toxicities of neuropathy, nausea and emesis, renal
failure, and bone marrow suppression are tolerable and can be prevented with medical measures.
It is hoped that local recurrence will be reduced with this approach with minimal added toxicity.
Progress: This protocol closed to patient entry in May 2000, with one patient enrolled who
remains disease free and continued to be followed at MAMC during FY06.
136
Detail Summary Sheet
Date: 30 Sep 06 Number: 98112 Status: Ongoing
Title: SWOG C9581: Phase III Randomized Study of Adjuvant Immunotherapy with Monoclonal
Antibody 17-lA Versus No Adjuvant Therapy Following Resection for Stage II (Modified Astler-
Coller B2) Adenocarcinoma
Principal Investigator: MAJ Jasmine T. Daniels, MC
Department: Medicine/Hematology & Oncology Facility: MAMC
Associate Investigator(s): MAJ Angela G. Mysliwiec, MC; LTC David E. McCune, MC; LTC
Tommy A. Brown, MC
Start - Completion: Funding: Periodic Review:
10/20/1998 - Indef SWOG via Henry M. Jackson Foundation 8/14/2006
Study Objective: (1) To determine whether adjuvant treatment with MoAb 17-lA will improve
the probability of overall and disease-free survival, and increase disease-free intervals in patients
who have undergone resection of a Stage II (pT3NO or pT4bNO) colon cancer, (2) to evaluate a
panel of prognostic markers, in order to correlate these measures with survival and recurrence
after adjuvant therapy in patients who have undergone resection of a Stage II (pT3NO or pT4bNO)
colon cancer. The specific aims of the companion study will be: (a) to determine whether
alterations in the expression of cell cycle related genes (thymidylate synthase, p53, and the cyclin-
dependent kinase inhibitors p21 and p27) predict the risk of survival and recurrence in this
patient population, (b) to determine whether alterations in markers of metastatic potential-
expression of DCC and measures of tumor angiogenesis (micro vascular density and vascular
endothelial growth factor expressionj-predict the risk of survival and recurrence in this patient
population, (c) to determine whether a marker of cellular differentiation-sucrase isomaltase-
predicts the risk of survival and recurrence in this patient population, and (d) to determine
whether interactions among these tumor markers identify subsets of patients with significantly
altered outcome.
Technical Approach: Subjects will be randomized and assigned to one of two treatment groups
following standard surgical removal of their tumor. Group 1 will receive standard care which is
surgery with no additional therapy after the tumor has been removed. Subjects will continue with
routine check-ups, doctor visits and test. Group 2 will receive five antibody treatments using MoAb
17-lA. Subjects will receive the drug by as an intravenous infusion over a 2-hour time period once
each 28 days. This 2-hour infusion will be repeated every 4 weeks for a total of 5 treatments.
During treatment, various blood tests and x-rays will be used to determine whether the disease
has returned. With subject's approval, tissue, body fluids, and other specimens obtained during the
normal course of treatment will be forwarded to a special research laboratory for storage and
scientific testing. Subjects will also be asked to complete a background information form to help
define groups of patient being treated.
Progress: This protocol closed to patient entry in May 2002, with one patient enrolled in FY98
who continued to be followed at MAMC during FY06.
137
Detail Summary Sheet
Date: 30 Sep 06 Number: 99014 Status: Ongoing
Title: SWOG C9741: A Randomized Phase III Trial of Sequential Chemotherapy Using
Doxorubicin, Paclitaxel, and Cyclophosphamide, or Concurrent Doxorubicin and
Cyclophosphamide Followed by Paclitaxel at 14 or 21 Day Intervals in Women with Node
Positive Stage II/IIIA Breast Cancer
Principal Investigator: MAJ Jasmine T. Daniels, MC
Department: Medicine/Hematology & Oncology Facility: MAMC
Associate Investigator(s): MAJ Angela G. Mysliwiec, MC; LTC David E. McCune, MC; LTC
Tommy A. Brown, MC
Start - Completion: Funding: Periodic Review:
1/26/1999 - Indef SWOG via Henry M. Jackson Foundation 11/21/2006
Study Objective: (1) To compare sequential chemotherapy with Doxorubicin, Paclitaxel, and
Cyclophosphamide to combined Doxorubicin and Cyclophosphamide followed by Paclitaxel for
disease-free and overall survival, (2) to determine whether increasing the dose density of adjuvant
chemotherapy (decreasing the interval between chemotherapy courses from 21 to 14 days) will
improve disease-free and overall survival, and (3) to compare the toxicity for patients treated with
sequential Doxorubicin, Paclitaxel, and Cyclophosphamide with toxicity for patients with
concurrent Doxorubicin plus Cyclophosphamide followed by Paclitaxel at 14 and 21 day intervals.
Technical Approach: This is a randomized comparison of several aggressive combination
chemotherapy regimens in the treatment of high-risk breast cancer due to positive lymph nodes. It
compares the current standard of care for node positive breast cancer with several more aggressive
variations. All patients will receive the same number of drugs and the same amount of drugs, but
the order in which the drugs are given and the time between treatments (2 weeks versus 3 weeks)
will be different. Arm 1, patients will receive Doxorubicin once every 3 weeks x 4 total doses
followed by Paclitaxel once every 3 weeks x 4 total doses followed by Cyclophosphamide once every
3 weeks x 4 total doses. Arm 2, patient will receive Doxorubicin once every 2 weeks x 4 total doses
followed by Paclitaxel once every 2 weeks x 4 total doses followed by Cyclophosphamide once every
2 weeks x 4 total doses. Arm 3, patients will receive Doxorubicin and Cyclophosphamide once
every 3 weeks x 4 total doses followed by Paclitaxel once every 3 weeks x 4 total doses. Arm 4,
patients will receive patients will receive Doxorubicin and Cyclophosphamide once every 2 weeks x
4 total doses followed by Paclitaxel once every 2 weeks x 4 total doses. G-CSF and Ciprofloxacin
will be given concurrent with each arm to help ameliorate side effects of the treatments.
Progress: This protocol closed to patient entry in March 1999, with three patients enrolled. One
patient is deceased and two patients remain disease free and continued to be followed at MAMC
during FY06.
138
Detail Summary Sheet
Date: 30 Sep 06 Number: 200036 Status: Ongoing
Title: SWOG E1199: A Phase III Study of Doxorubicin-Cyclophosphamide Therapy Followed by
Paclitaxel or Docetaxel Given Weekly or Every 3 Weeks in Patients with Axillary Node-Positive
Breast Cancer
Principal Investigator: MAJ Jasmine T. Daniels, MC
Department: Medicine/Hematology & Oncology Facility: MAMC
Associate Investigator(s): MAJ Angela G. Mysliwiec, MC; LTC David E. McCune, MC; LTC
Tommy A. Brown, MC
Start - Completion: Funding: Periodic Review:
8/29/2000 - Indef SWOG via Henry M. Jackson Foundation 1/4/2006
Study Objective: (1) To determine whether docetaxel improves disease-free survival and overall
survival when compared to paclitaxel following 4 cycles of doxorubicin-cyclophosphamide therapy
(2) To determine whether weekly administration of taxanes (paclitaxel or docetaxel) for 12 weeks
improves disease-free survival and overall survival when compared with the conventional (every 3
weeks) schedule for 4 cycles following 4 cycles of doxorubicin-cyclophosphamide therapy (3) To
compare the toxicity of docetaxel given weekly for 12 weeks to that of paclitaxel given every 3
weeks for 4 cycles (4) To compare the toxicity of paclitaxel given weekly for 12 weeks for 4 cycles
to that of docetaxel given every 3 weeks for 4 cycles (5) To compare the toxicity of paclitaxel given
every 3 weeks for 4 cycles to that of docetaxel given every 3 weeks for 4 cycles and (6) To compare
the toxicity of paclitaxel given weekly for 12 weeks to that of docetaxel given weekly for 12 weeks.
Technical Approach: This study compares aggressive chemotherapy schedules to standard of
care for high risk node positive breast cancer. Eligible patients will be randomized into one of four
treatment arms: Arm A, 12 weeks of Adriamycin and Cytoxan followed by 12 weeks of Taxol (the
standard treatment); Arm B, 12 weeks of Adriamycin and Cytoxan followed by 12 weeks of Taxol
(lower dose than standard); Arm C, 12 weeks of Adriamycin and Cytoxan followed by 12 weeks of
Taxotere (medium dose); and Arm D, 12 weeks of Adriamycin and Cytoxan followed by 12 weeks of
Taxotere (low dose).
All Arms will receive Adriamycin and cyclophosphamide, IV once every 3 weeks for 4 cycles. Then
Arm A will receive Taxol, IV once every 3 weeks for 4 treatments. Arm B will receive Taxol IV once
a week for 12 weeks of treatment. Arm C will receive Taxotere IV once every 3 weeks for 4
treatments. Arm D will receive Taxotere once a week for 12 weeks of treatment.
Progress: This protocol closed to patient entry in January 2002, with fourteen patients enrolled.
One patient died and thirteen remain disease free and continued to be followed at MAMC during
FY06.
139
Detail Summary Sheet
Date: 30 Sep 06 Number: 99071 Status: Ongoing
Title: SWOG E2197: Phase III Study of Adriamycin/Taxotere vs. Adriamycin/Cytoxan for the
Adjuvant Treatment of Node Positive or High Risk Node Negative Breast Cancer
Principal Investigator: MAJ Jasmine T. Daniels, MC
Department: Medicine/Hematology & Oncology Facility: MAMC
Associate Investigator(s): MAJ Angela G. Mysliwiec, MC; LTC David E. McCune, MC; LTC
Tommy A. Brown, MC
Start - Completion: Funding: Periodic Review:
7/20/1999 - Indef SWOG via Henry M. Jackson Foundation 4/20/2006
Study Objective: To determine whether Adriamycin/Taxotere will improve disease-free survival
and overall survival when compared to Adriamycin/Cytoxan in lymph node positive (1-3 positive
nodes) and high risk lymph node negative breast cancer. To compare toxicity of
Adriamycin/Taxotere to Adriamycin/Cytoxan.
Technical Approach: This is multi-site study with randomization to one of two arms:
Adriamycin/Taxotere (AT) or Adriamycin/Cytoxan (AC). The dosages for the AT group: Adriamycin
60 mg/M2 IV and Taxotere 60 mg/M2 IV over 1 hour infusion every 3 weeks x 4 cycles. Cipro 500
mg PO b.i.d. starting Day 8 and continuing x 10 days. If a patient is allergic to Cipro, an
alternative broad spectrum antibiotic may be used. Decadron 8 mg PO b.i.d., beginning one day
prior to treatment with Taxotere and continued for two additional days; repeat q 3 weeks x 4
cycles. The dosages for the AC group: Adriamycin 60 mg/m2 IV and Cytoxan 600 mg/ml IV. Every
3 weeks x 4 cycles. In both groups, post-menopausal patients who are ER and/or PR positive will
receive Tamoxifen 20 mg PO daily x 5 years at the completion of chemotherapy. G-CSF: Patients
who have an episode of febrile neutropenia should be placed on G-CSF according to ASCO
Guidelines. Patients who have febrile neutropenia after a subsequent dose of chemotherapy in
spite of G-CSF should have the chemotherapy doses lowered by 25%.
Progress: This protocol closed to patient entry in January 2000, with two patients enrolled who
continued to be followed at MAMC during FY06.
140
Detail Summary Sheet
Date: 30 Sep 06 Number: 204066 Status: Ongoing
Title: SWOG E2496 Randomized Phase III Trial of ABVD Versus Stanford V +/- Radiation
Therapy in Locally Extensive and Advanced Stage Hodgkin's Disease With 0-2 Risk Factors
Principal Investigator: MAJ Jasmine T. Daniels, MC
Department: Medicine/Hematology & Oncology Facility: MAMC
Associate Investigator(s): MAJ Angela G. Mysliwiec, MC; LTC David E. McCune, MC; LTC
John B. Halligan, MC; LTC William B. Reece, MC
Start - Completion: Funding: Periodic Review:
8/17/2004 - Apr 2009 SWOG via Henry M. Jackson Foundation 5/23/2006
Study Objective: (1) To compare the failure-free survival in patients with locally extensive and
advanced stage Hodgkin's \disease d(HD) treated with standard ABVD chemotherapy +
radiotherapy versus patients given Stanford V chemotherapy +radiotherapy. (2) To assess overall
survival and freedom from progression in these patients at 5 and 10 years. (3) To assess secondary
endpoints: pulmonary function, incidence of second cancers, reproductive function (at baseline and
at 5 years) and deaths from causes other than Hodgkin's disease.
Technical Approach: SWOG E2496 is a national intergroup randomized Phase III trial of two
treatment regimens for the treatment of locally extensive and advanced stage Hodgkin's disease.
Subjects with bulky disease will receive radiation therapy in addition to chemotherapy in the
control ABVD treatment Arm and subjects with lymphoma masses > 5 cm will receive radiation
therapy on the Stanford V Arm. The primary endpoint of the trial is failure free survival.
Laboratory endpoints include relative risk of death and treatment failure in subjects with EBV-
positive disease, the concordance between three different EBV detection techniques, and the
relationship of EBV viral DNA clearance for the two treatment arms. Laboratory studies will also
investigate the relationship between T-cell response and EBV status and the time course of the T-
cell response. This is a national intergroup study expected to accrue 204 subjects per year for a
total of 850 subjects. At MAMC 2 subjects per year are expected to enroll. Data and statistical
analysis will be conducted by the sponsoring study group, ECOG (Eastern Cooperative Oncology
Group) with planned interim analyses at 33% and 67% of the number of anticipated treatment
failures. It is expected that 3 years of follow-up will be required after complete accrual.
Progress: This protocol closed to enrollment in April 2006; four patients enrolled at MAMC. Three
patients remain in follow-up and one transferred to another facility.
141
Detail Summary Sheet
Date: 30 Sep 06 Number: 200040 Status: Ongoing
Title: SWOG E4494: Phase III Trial of CHOP versus CHOP and Chimeric Anti-CD20
Monoclonal Antibody (IDEC-C2B8) in Older Patients with Diffuse Mixed, Diffuse Large Cell and
Immunoblastic Large Cell Histology Non-Hodgkin's Lymphoma
Principal Investigator: MAJ Jasmine T. Daniels, MC
Department: Medicine/Hematology & Oncology Facility: MAMC
Associate Investigator(s): MAJ Angela G. Mysliwiec, MC; LTC David E. McCune, MC; LTC
Tommy A. Brown, MC
Start - Completion: Funding: Periodic Review:
1/25/2000 - Indef SWOG via Henry M. Jackson Foundation 1/4/2006
Study Objective: (1) To compare CHOP treatment with or without chimeric anti-CD20
monoclonal antibody (IDEC-C2B8) in elderly patients with diffuse mixed, diffuse large cell, and
immunoblastic large cell non-Hodgkin's lymphoma of B lineage with respect to response rate, the
time to treatment failure, toxicity and survival, (2) To compare IDEC-C2B8 monoclonal antibody
as maintenance therapy to observation alone after CHOP chemotherapy with respect to time to
treatment failure, duration of response, toxicity and survival after an initial response to induction
therapy of CHOP + IDEC-C2B8, and (3) To determine if maintenance therapy with IDEC-C2B8
results in the conversion of any partial responses to a complete response.
Technical Approach: This study adds a new drug, chimeric anti-CD20 monoclonal antibody, to
the standard treatment (cyclophosphamide, doxorubicin, vincristine and prednisone, CHOP) of
Non-Hodgkin's Lymphoma. Patients eligible for this study will be randomized to receive or not to
receive IDEC-C2B8 (anti-CD20) in conjunction with chemotherapy. Treatment Arm A, CHOP plus
Anti-CD20 will receive the study drug IV over 6 to 12 hours on Days 7 and 3 before the first
treatment cycle of CHOP. Anti-CD20 will also be given 48 hours prior to cycles 3, 5 and 7 of CHOP
Treatment Arm B will receive CHOP for a minimum of 6 or a maximum of 8 cycles. Restaging of
disease after 4 cycles and again after 6 cycles will be done to determine response and eligibility to
be randomized to Maintenance Treatment Arms C & D. Arm C will continue to receive Anti-CD20
IV, four weekly doses every 6 months for 2 years. Arm D will be the observation group.
Progress: This protocol closed to patient entry in May 2001, with two patients enrolled. One
patient died and the other patient continued to be followed at MAMC during FY06.
142
Detail Summary Sheet
Date: 30 Sep 06 Number: 202010 Status: Ongoing
Title: SWOG E5597: Phase III Chemoprevention Trial of Selenium Supplementation in Persons
with Resected Stage I Non-Small Cell Lung Cancer
Principal Investigator: MAJ Jasmine T. Daniels, MC
Department: Medicine/Hematology & Oncology Facility: MAMC
Associate Investigator(s): MAJ Angela G. Mysliwiec, MC; LTC David E. McCune, MC; LTC
Tommy A. Brown, MC
Start - Completion: Funding: Periodic Review:
10/23/2001 - Oct 2005 SWOG via Henry M. Jackson Foundation 8/22/2006
Study Objective: (1) To evaluate the efficacy of selenium supplementation in reducing the
incidence of second primary lung tumors in patients who have been treated for Stage I non-small
cell cancer with complete surgical resection, (2) to evaluate the qualitative and quantitative
toxicity of a selenium supplementation in a daily administration schedule and (3) to compare the
incidence of specific cancers and mortality from cancer as well as overall survival of patients
treated with selenium supplementation versus patients treated with placebo.
Technical Approach: Selenium chemo-prevention may improve upon patients with high risk of
second lung primaries as well other aero digestive tract tumors.
Progress: This protocol remains open to patient entry, with two patients enrolled at MAMC. Both
patients remain on active study treatment.
143
Detail Summary Sheet
Date: 30 Sep 06 Number: 202012 Status: Ongoing
Title: SWOG G0182: A Phase III Randomized Trial of Paclitaxel and Carboplatin Versus Triplet
or Sequential Doublet Combinations in Patients with Epithelial Ovarian or Primary Peritoneal
Carcinoma
Principal Investigator: MAJ Jasmine T. Daniels, MC
Department: Medicine/Hematology & Oncology Facility: MAMC
Associate Investigator(s): MAJ Angela G. Mysliwiec, MC; LTC David E. McCune, MC; LTC
Jane Shen-Gunther, MC; LTC Tommy A. Brown, MC
Start - Completion: Funding: Periodic Review:
10/23/2001 - Nov 2004 SWOG via Henry M. Jackson Foundation 9/29/2006
Study Objective: (1) To compare the efficacy of each experimental arm with the control arm
(paclitaxel and Carboplatin). Efficacy will be determined through analysis of overall survival and
progression-free survival, (2) To compare the response rate in patients with measurable disease,
toxicities and complications of each treatment regimen and to describe dose-intensity and
cumulative dose delivery for each regimen and (3) To extend the accrual into a study initiated with
GOG Protocol #0172 which will assess whether inactivated BRCAl and /or BRCA2 is a prognostic
factor for clinical outcome.
Technical Approach: This study is designed to compare the effectiveness and side effects of
several chemotherapy combinations (Paclitaxel, Carboplatin, Gemcitabine, Topotecan, Doxil
[Liposomal Doxorubicin]) which are known to be effective in women with ovarian or primary
peritoneal cancer. This study will enroll adult females with histologic diagnosis of primary
peritoneal carcinoma or epithelial ovarian carcinoma, Stage III or IV, with either optimal or
suboptimal residual disease following initial surgery.
Progress: This study closed to patient entry in September 2004, with eight patients enrolled.
Three patients continued to be followed at MAMC during FY06.
144
Detail Summary Sheet
Date: 30 Sep 06 Number: 97070 Status: Ongoing
Title: SWOG JBR.10 (NCIC CTG BR.10): A Phase III Prospective Randomized Study of
Adjuvant Chemotherapy with Vinorelbine and Cisplatin in Completely Resected Non-small Cell
Lung Cancer with Companion Tumour
Principal Investigator: MAJ Jasmine T. Daniels, MC
Department: Medicine/Hematology & Oncology Facility: MAMC
Associate Investigator(s): MAJ Angela G. Mysliwiec, MC; LTC David E. McCune, MC; LTC
Tommy A. Brown, MC
Start - Completion: Funding: Periodic Review:
3/21/1997 - Indef SWOG via Henry M. Jackson Foundation 2/22/2006
Study Objective: 1) To compare the duration of overall survival (OS) between completely rejected
patients with T2 NO, T1-2N1 non-small cell lung cancer (NSCLC) who have received either
adjuvant chemotherapy with vinorelbine and cisplatin or observation alone. 2) To determine
disease-free survival. 3) To confirm the prognostic significance of ras mutations when present in
the primary tumor. 4) To provide a comprehensive tumor bank linked to a clinical data base for the
further study of molecular markers in rejected NSCLC. 5) To measure and compare health related
quality of life in both treatment arms throughout the study period. 6) To evaluate toxicity related
to chemotherapy.
Technical Approach: The role of adjuvant chemotherapy in Non-small cell lung cancer is
controversial. Most clinical trials have shown no benefit to adjuvant chemotherapy. In the early
80's the lung cancer study group showed some benefit with combination chemotherapy in terms of
survival, however, the control arm was not a strict observational arm and contained a "biological
response modifier" in it. Thus with recent improved survival in Stage IV lung cancer shown
compared to observation, it is assumed that using platinum based therapies may enhance survival
in patients that have completely rejected non-small cell lung cancer. In patients with rejected
Stage I, II, and III Non-small cell lung cancer it is known that the long term survival rates are 50
to 60%, 30 to 50%, and 19 to 49% respectively. It is thus the aim of this study to assess whether
adjuvant therapy with Cisplatin and Vinorelbine will improve survival and relapse free survival
compared to observation. In addition to the above study, tissue samples will be sent to the
University of Washington for evaluation of Ras mutations to assess its prognostic importance.
Progress: This protocol closed to patient entry in April 2001, with two patients enrolled who
remain disease free and continued to be followed at MAMC during FY06.
145
Detail Summary Sheet
Date: 30 Sep 06 Number: 99040 Status: Ongoing
Title: SWOG JMA.17: A Phase III Randomized Double-Blinded Study of Letrozole Versus
Placebo in Women with Primary Breast Cancer Completing Five or More Years of Adjuvant
Tamoxifen
Principal Investigator: MAJ Jasmine T. Daniels, MC
Department: Medicine/Hematology & Oncology Facility: MAMC
Associate Investigator(s): MAJ Angela G. Mysliwiec, MC; LTC David E. McCune, MC; LTC
Tommy A. Brown, MC
Start - Completion: Funding: Periodic Review:
2/23/1999 - Indef SWOG via Henry M. Jackson Foundation 1/24/2006
Study Objective: Primary: To determine the disease-free survival and overall survival (all cause
mortality) for women who have previously received >= 5 years of adjuvant Tamoxifen, randomized
to receive wither Letrozole 2.5 mg daily or placebo daily for 5 years.
Secondary: To evaluate the incidence of contralateral breast cancer. To evaluate the long term
clinical and laboratory safety of Letrozole with special attention to: lipid profile as assessed by
blood sampling (in a limited number of centers), cardiovascular morbidity and mortality (i.e.
significant coronary heart disease, which includes myocardial infarctions and angina requiring
percutaneous transluminal coronary angioplasty or coronary artery bypass graft, fatal and
nonfatal strokes and all vascular deaths) as assessed by reported toxicity, the incidence of all bone
fractures (with particular emphasis on hip and wrist fractures as indicators of osteoporosis) as
assessed by reported toxicity, changes in bone density (in a limited number of centers), common
toxicities as assessed by reported toxicity.
Third: To evaluate overall quality of life.
Technical Approach: This is a multi-centre, double-blind, placebo-controlled parallel randomized
trial of the NCIC Clinical Trials Group, supported by Novartis. Patients will be stratified by:
receptor status at diagnosis (positive, unknown), lymph node status at diagnosis (negative,
positive, unknown), and a prior adjuvant chemotherapy (yes, no). Patients will be centrally
randomized to receive one of the following treatments: Arm 1 (letrozole): 2.5 mg po daily x 5 years
or Arm 2 (Placebo): po daily x 5 years.
Progress: This protocol closed to patient entry in December 2005, with thirteen patients enrolled;
two patients continue on Letrozole. One patient is deceased; twelve patients continued to be
followed at MAMC during FY06.
146
Detail Summary Sheet
Date: 30 Sep 06 Number: 200120 Status: Ongoing
Title: SWOG N9831: Phase III Trial of Doxorubicin and Cyclophosphamide (AC) Followed by
Weekly Paclitaxel With or Without Trastuzumab as Adjuvant Treatment for Women with HER-2
Over-expressing or Amplified Node Positive or High-Risk Node Negative Breast Cancer (an
Intergroup Study)
Principal Investigator: MAJ Jasmine T. Daniels, MC
Department: Medicine/Hematology & Oncology Facility: MAMC
Associate Investigator(s): MAJ Angela G. Mysliwiec, MC; LTC David E. McCune, MC; LTC
Tommy A. Brown, MC
Start - Completion: Funding: Periodic Review:
8/22/2000 - Dec 2005 SWOG via Henry M. Jackson Foundation 7/18/2006
Study Objective: (1) To compare the combination AC followed by weekly paclitaxel with the
sequential schedule of the combination of AC, weekly paclitaxel, and trastuzumab in terms of
disease-free survival (DFS). (2) To compare the combination of AC followed by weekly paclitaxel
with the combination of AC followed by the combination of weekly paclitaxel and trastuzumab in
terms of DFS. (3) To compare the sequential schedule of AC, weekly paclitaxel, and trastuzumab
with the combination of weekly paclitaxel and trastuzumab in terms of DFS. (4) To compare the
cardiotoxicities of (a) AC followed by weekly paclitaxel, (b) AC followed by weekly paclitaxel
followed by weekly trastuzumab, and (c) AC followed by weekly paclitaxel and trastuzumab
followed by weekly trastuzumab.
Technical Approach: Subjects will be randomly assigned to one of three arms: Arm A -
Adriamycin and Cytoxan (AC) by vein over about 30 minutes one day every three weeks for a total
of four treatments. After all treatment with AC is done (about week 12), Taxol by vein over 1 hour
one day every week for a total of 12 treatments. Total length of treatment will be about six
months. Arm B - Subjects will be given Adriamycin and Cytoxan (AC) by vein over about 30
minutes one day every three weeks for a total of four treatments. After all treatment with AC is
done (about week 12), you will get Taxol by vein over 1 hour one day every week for a total of 12
treatments. After all treatment with Taxol is done (about week 24), Herceptin by vein one day
every week for one year. The first dose of Herceptin will be given over about 90 minutes. Subjects
will be watched for 1 hour after the first dose of Herceptin. If they do well this first dose, other
doses will be given over about 30 minutes. Total length of treatment will be about 18 months. Arm
C - Subjects will be given Adriamycin and Cytoxan (AC) by vein over about 30 minutes one day
every three weeks for a total of four treatments. After all treatment with AC is done (about week
12), subjects will be given Taxol, by vein over 1 hour, plus Herceptin, by vein one day every week,
for a total of 12 treatments. After all treatment with Taxol plus Herceptin is done (about week 23),
subjects will get Herceptin alone one day every week for six months. The first dose of Herceptin
will be given over about 90 minutes. You will be watched for 1 hour after the first dose of
Herceptin. If subjects do well this first dose, other doses will be given over about 30 minutes. Total
length of treatment will be about one year.
Regardless of which treatment, at the end of all chemotherapy, subject may also get Tamoxifen, if
estrogen or progesterone receptor positive, for five years. If subjects had a lumpectomy, they will
also get radiation therapy after chemotherapy has ended. Blood samples will be taken before the
start treatment for research use. Subjects will be followed indefinitely.
Progress: This protocol closed to patient entry in April 2005, with nine patients enrolled. One
patient's death was unrelated to study participation, two patients removed from the study due to
147
decreases in LVF, and the remaining six patients completed study treatment. Eight patients
continued to be followed at MAMC during FY06.
148
Detail Summary Sheet
Date: 30 Sep 06 Number: 201136 Status: Completed
Title: SWOG S0009: A Phase II Evaluation of Neoadjuvant Chemotherapy, Interval Debulking
Followed by Intraperitoneal Chemotherapy in Women with Stage III and IV Epithelial Ovarian
Cancer, Fallopian Tube Cancer or Primary Peritoneal Cancer
Principal Investigator: MAJ Jasmine T. Daniels, MC
Department: Medicine/Hematology & Oncology Facility: MAMC
Associate Investigator(s): MAJ Angela G. Mysliwiec, MC; LTC David E. McCune, MC; LTC
Tommy A. Brown, MC; LTC Jane Shen-Gunther, MC
Start - Completion: Funding: Periodic Review:
9/25/2001 - Aug 2004 SWOG via Henry M. Jackson Foundation 8/24/2005
Study Objective: (1) To evaluate the overall survival and progression-free survival in Stage III or
IV epithelial ovarian, fallopian tube or primary peritoneal carcinoma patients with bulky disease
and/or malignant pleural effusions treated with neoadjuvant intravenous paclitaxel and
Carboplatin, cytoreductive surgery and intravenous/intraperitoneal paclitaxel and intraperitoneal
Carboplatin, (2) To estimate the percent of patients successfully cytoreduced to optimal disease (<1
cm residual) following neoadjuvant chemotherapy, (3) To evaluate the toxicities associated with
this therapy, and (4) To explore the relationship between tumor p53 expression, cellular
proliferation rate as measured by PCNA and apoptotic rate, and human tumor cloning assay
results at time of debulking surgery with progression-free survival and overall survival in patients
undergoing cytoreductive surgery.
Technical Approach: This protocol evaluates the effectiveness and side effects of a treatment
regimen for advanced ovarian, peritoneal, and fallopian tube cancers. The treatment consists of
intravenous chemotherapy of paclitaxel and carboplatin (3 treatments), followed by surgery,
followed by a combination of intravenous paclitaxel and intra-peritoneal carboplatin and paclitaxel
(6 treatments).
Progress: This protocol closed enrollment in February 2006, when accrual goals were met. No
subjects enrolled at MAMC.
149
Detail Summary Sheet
Date: 30 Sep 06 Number: 201137 Status: Ongoing
Title: SWOG S0012: A Comparative Randomized Study of Standard Doxorubicin and
Cyclophosphamide Followed by Weekly Paclitaxel Vs. Weekly Doxorubicin and Daily Oral
Cyclophosphamide Plus G-CSF Followed by Weekly Paclitaxel as Neoadjuvant Therapy for
Inflammatory and Locally Advanced Breast Cancer
Principal Investigator: MAJ Jasmine T. Daniels, MC
Department: Medicine/Hematology & Oncology Facility: MAMC
Associate Investigator(s): MAJ Angela G. Mysliwiec, MC; LTC David E. McCune, MC; LTC
Tommy A. Brown, MC
Start - Completion: Funding: Periodic Review:
9/25/2001 - Oct 2004 SWOG via Henry M. Jackson Foundation 8/29/2006
Study Objective: (1) To compare the microscopic pathologic response rates in patients with
inflammatory and estrogen-receptor negative locally advanced breast cancer treated with weekly
Doxorubicin and daily oral Cyclophosphamide given with G-CSF support to in-patients treated
without "standard" Doxorubicin and Cyclophosphamide regimen given every three weeks, (2) To
compare the toxicities of these two regimens, (3) To compare the delivered dose intensity of these
two regimens, and (4) To assess the association between microscopic pathologic complete response
and clinical complete response at the primary tumor site in these patients.
Technical Approach: This trial is designed to compare two different treatment regimens for
breast cancer prior to surgery to see if one works better against breast cancer than the other in
very poor risk patients who may benefit from up-front chemotherapy. The standard regimen of
Adriamycin and Cyclophosphamide given Day 1 every 21 days is compared to a regimen of
Adriamycin given once a week for 15 weeks and oral Cyclophosphamide daily for 15 weeks.
Filgrastim and trimethoprim sulfa will also be given in this regimen to protect against toxicity of
the chemotherapy agents used.
Progress: This protocol remains open to patient entry, with three patients enrolled. One patient is
deceased and two continued to be followed at MAMC in FY06. No internal adverse events were
reported and no patients received study treatment in the past year.
150
Detail Summary Sheet
Date: 30 Sep 06 Number: 203084 Status: Ongoing
Title: SWOG S0016, A Phase III Trial of CHOP + Rituximab vs. CHOP + Iodine- 131-Labeled
Monoclonal Anti-Bl Antibody (Tositumomab) for Treatment of Newly Diagnosed Follicular Non-
Hodgkin's Lymphomas
Principal Investigator: MAJ Jasmine T. Daniels, MC
Department: Medicine/Hematology & Oncology Facility: MAMC
Associate Investigator(s): MAJ Angela G. Mysliwiec, MC; LTC David E. McCune, MC; LTC
Tommy A. Brown, MC
Start - Completion: Funding: Periodic Review:
10/29/2003 - Jul 2006 SWOG via Henry M. Jackson Foundation 5/23/2006
Study Objective: (1) To compare progression-free and overall survival between CHOP-Rituximab
vs. CHOPP+I-131 tositumomab. (2) To compare the response rate between CHOP-Rituximab vs.
CHOPP+I-131.(3) To compare the toxicities of these two regimens. Also, to compare the molecular
remission rates by measuring colonel rearrangements in the bone marrow at baseline and at one
year post-treatment.
Technical Approach: This is a national trial with a goal accrual of 500 patients to determine if a
radioisotope labeled Anti-CD20 antibody (tositumomab) added to standard CHOP chemotherapy is
superior to a combination of CHOP plus the uncongealed anti-CD20 antibody Rituximab.
Specifically the endpoints will include disease free survival, overall survival, response rate, rate of
molecular remission and data will also be collected or the toxicity of therapy. Data analysis will be
analyzed by the SWOG Data and Safety Monitoring Committee (DSMC). The power analysis by
the SWOG DSMC includes a sample size of 250 per treatment arm will detect a response rate
difference of 6% between treatments. Eligible subjects will be randomized into one of the two study
arms. (1) CHOP chemotherapy plus the rituximab antibody, 6, 21 day treatment cycles or (2)
CHOP chemotherapy followed by the 1-131 anti-Bl antibody, tositumomab, 6, 21 day treatment
cycles. Four to six weeks after completion of chemotherapy, subjects will receive treatment with by
the 1-131 anti-Bl antibody, tositumomab. Also, at the time of surgery, tumor tissue, tumor fluid,
and blood will be collected and used for specific experimental molecular tests, called P53, PCNA,
Apoptosis and Human tumor cloning assay.
Progress: This protocol is open to enrollment, with three subjects enrolled who completed
treatment. One subject is deceased due to progressive disease; two remain in remission and
continued on follow-up during FY06.
151
Detail Summary Sheet
Date: 30 Sep 06 Number: 204052 Status: Completed
Title: SWOG S0023, A Phase III Trial of Cisplatin/Etoposide/Radiotherapy with Consolidation
Docetaxel Followed by Maintenance Therapy with ZD1839 or Placebo in Patients With
Inoperable Locally Advanced Stage III Non- Small Cell Lung Cancer
Principal Investigator: MAJ Jasmine T. Daniels, MC
Department: Medicine/Hematology & Oncology Facility: MAMC
Associate Investigator(s): MAJ Angela G. Mysliwiec, MC; LTC David E. McCune, MC; LTC
John B. Halligan, MC; LTC William B. Reece, MC; LTC Tommy A. Brown, MC
Start - Completion: Funding: Periodic Review:
11/15/2004 - Apr 2010 SWOG via Henry M. Jackson Foundation 2/28/2006
Study Objective: (1) To assess whether maintenance therapy with ZD 1839 as compared to
placebo following induction cisplatin/etoposide/radiotherapy plus consolidation docetaxel improves
overall survival and progression-free survival in patients with unresectable Stage III non-small
cell lung cancer (NSCLC). (2) To describe the toxicity profile of long term administration of
ZD1839. To obtain samples for correlative studies as outlined in S9925.
Technical Approach: This study is an intergroup Phase III randomized, placebo-controlled trial
of a standard chemotherapy / radiation therapy regimen for inoperable Stage III NSCLC followed
by randomization to maintenance ZD1839 (Iressa) versus placebo for 5 years. This national trial
has a goal accrual of 840 over 3.5 years or about 240 patients per year with 3 patients per year at
MAMC. The major end-points of the trial are progression-free survival and overall survival. Data
analysis will be conducted by the SWOG monitoring committee with a planned interim analysis
after 400 patients have been accrued to see if pre-determined criteria for early termination of the
study have been met. The trial is powered to defect a 33% increase in median survival of the
treatment arm.
Progress: This protocol closed to enrollment, with three patients enrolled; all deceased due to
progressive disease. A closure letter will be submitted to permanently close study site.
152
Detail Summary Sheet
Date: 30 Sep 06 Number: 204123 Status: Ongoing
Title: SWOG S0106, A Phase III Study of the Addition of Gemtuzumab Ozogamicin (Mylotarg®)
Induction Therapy Versus Standard Induction With Daunomycin and Cytosine Arabinoside
Followed by Consolidation and Subsequent Randomization to Post-Consolidation Therapy With
Gemtuzumab Ozogamicin (Mylotarg®) or No Additional Therapy for Patients Under Age 56
With Previously Untreated DeNovo Acute Myeloid Leukemia (AML)
Principal Investigator: MAJ Jasmine T. Daniels, MC
Department: Medicine/Hematology & Oncology
Facility: MAMC
Associate Investigator(s): MAJ Angela G. Mysliwiec, MC; LTC David E. McCune, MC
Start - Completion: Funding:
3/21/2005 - Jan 2012 SWOG via Henry M. Jackson Foundation
Periodic Review:
9/29/2006
Study Objective: (1) To compare disease-free survival (DS) of patients under age 56 with
previously untreated, de novo, non-M3, MAL who received gemtuzumab ozogamicin as post¬
consolidation therapy versus patients who received no post-consolidation therapy. (2) To compare
the complete remission (CR) rate achieved by the addition of gemtuzumab ozogamicin to standard
induction chemotherapy to that achieved with standard induction chemotherapy in patients under
the age of 56 with previously untreated, de novo, non-M-3 AML. The durability of complete
response will also be measured. (3) To estimate the frequency and severity of toxicities of the
addition of gemtuzumab ozogamicin to induction therapy and post consolidation therapy. (4) To
evaluate the prognostic significance of CD33 expression on the response rate of those patients who
receive gemtuzumab ozogamicin. (5) To evaluate the prognostic significance of FLT3 mutations
prior to therapy, and of minimal residual disease in remission specimens collected before and after
consolidation therapy and after post-consolidation therapy with gemtuzumab ozogamicin. (6) To
evaluate the prognostic significance of the flow cytometric detection of minimal residual disease in
specimens collected before and after consolidation therapy and after post-consolidation therapy
with gemtuzumab ozogamicin.
Technical Approach: This is a randomized phase III trial comparing standard induction
chemotherapy for AML with or without the anti-leukemia monoclonal antibody Gemtuzumab
ozogamicin (Mylotarg®). Patients will be further randomized for post-consolidation treatment with
Gemtuzumab ozogamicin (Mylotarg®) versus no post-consolidation treatment. Due to enhanced
toxicity in older patients, this trial is limited to adult patients less than age 56 at the time of study
entry. The end points of the trial are to compare disease free survival, complete remission rates
and to determine toxicities of each treatment Arm. The trial will also investigate the prognostic
significance of CD33 expression, FLT-3 mutations, and the flow cytometric detection of minimal
residual disease. The goal accrual of this trial is 684 patients over 5 years with an expected
enrollment of 2 patients per year at MAMC.
Progress: This protocol remains open to enrollment with no patients enrolled during FY06.
153
Detail Summary Sheet
Date: 30 Sep 06 Number: 204034 Status: Ongoing
Title: SWOG S0221, Phase III Trial of Continuous Schedule AC + G Vs. Q 2 Week Schedule AC,
Followed by Paclitaxel Given Either Every 2 Weeks or Weekly for 12 Weeks as Post-Operative
Adjuvant Therapy in Node-Positive or High-Risk Node-Negative Breast Cancer
Principal Investigator: MAJ Jasmine T. Daniels, MC
Department: Medicine/Hematology & Oncology
Facility: MAMC
Associate Investigator(s): MAJ Angela G. Mysliwiec, MC; LTC David E. McCune, MC
Start - Completion: Funding:
2/26/2004 - Indef SWOG via Henry M. Jackson Foundation
Periodic Review:
1/24/2006
Study Objective: (1) To compare the disease-free survival of patients with node-positive or high-
risk node-negative breast cancer treated with the combination of doxorubicin and
cyclophosphamide given every 2 weeks with Pegfilgrastim support with that of patients treated
with weekly doxorubicin and daily oral cyclophosphamide with filgrastim support, with both
treatments to be followed by paclitaxel given according to one of two schedules. (2) To compare the
disease-free survival of patients with node-positive or high-risk node-negative breast cancer
treated with either 12 weeks of weekly paclitaxel or paclitaxel given every 2 weeks with
Pegfilgrastim support for 6 cycles following treatment with one of the two
doxorubicin/cyclophosphamide regimens discussed above. (3) To compare the overall survival
produced by the four treatment arms. (4) To compare the toxicity of the four treatment arms. (5)
To examine the association of putative prognostic markers with outcome and the interaction of
these markers with treatment.
Technical Approach: This is a 4-arm phase III randomized trial of two different dose- dense
doxorubicin plus cyclophosphamide chemotherapy regimens followed by two different schedules of
taxol administration used for the treatment of node positive and high risk node negative breast
cancer. Major endpoints of the trial are disease free survival and overall survival with an
anticipated accrual of 2000 patients per year for a goal of 4500 patients accrued over 2.2 years.
The study DSMC will perform an interim analysis at years 2.5, 4 and 6.
Progress: This protocol is open to enrollment with 16 patients enrolled. One patient is deceased
and the others remain on treatment.
154
Detail Summary Sheet
Date: 30 Sep 06 Number: 204094
Status: Ongoing
Title: SWOG S0226, Phase III Randomized Trial of Anastrozole Versus Anastrozole and
Fulvestrant as First Line Therapy for Post Menopausal Women With Metastatic Breast Cancer
Principal Investigator: MAJ Jasmine T. Daniels, MC
Department: Medicine/Hematology & Oncology
Facility: MAMC
Associate Investigator(s): MAJ Angela G. Mysliwiec, MC; LTC David E. McCune, MC
Start - Completion: Funding:
9/29/2004 - Jun 2010 SWOG via Henry M. Jackson Foundation
Periodic Review:
6/6/2006
Study Objective: (1) To compare time to tumor progression in post-menopausal women with
metastatic breast cancer treated with Anastrozole versus Anastrozole and Fulvestrant. (2) To
compare clinical benefit (CR, PR, confirmed or unconfirmed, or stable disease >24 weeks) and
overall survival for this cohort of patients. (3) To assess the adverse events of Anastrozole as
compared to Anastrozole and Fulvestrant in this cohort of patients. (4) To assess the prognostic
significance of subtypes of ER positive and HER-2 status. (5) To assess parameters of estrogen and
clinical pharmacology and estrogen levels as outlined in Sec. 15.4. (6) To compare the Anastrozole
plasma levels on each treatment arm at 8 weeks, 16 weeks and 24 weeks after randomization.
Technical Approach: S0226 is a randomized Phase III trial of Anastrozole versus Anastrozole
plus Fulvestrant as first line endocrine therapy for metastatic breast cancer. The end-points of the
trial are to assess the time to tumor progression of each of these treatments, to assess response
rates and to assess overall survival of patients. The trial will also assess the adverse effects of each
treatment arm and the prognostic significance of tumor ER status and HER2 status.
Pharmacokinetic data on Anastrozole plasma levels and serum estradiol levels will be measured in
both treatment groups. The trial has a national goal accrual of 230 patients per year for 3 years,
with a goal accrual of 5 patients per year here at Madigan. All data evaluation will be done
through the SWOG. There will be a planned interim analysis of progression free survival after 50%
and 75% of national goal accrual.
Patients will be randomized to receive either 1 mg Anastrozole by mouth every day or 1 mg
Anastrozole orally every day and 250 mg of Fulvestrant intramuscular injection once every 28
days. This schedule will continue until disease worsens or side effects are unacceptable.
Fulvestrant may be given if disease worsens and if other treatment is not required right away. The
first fifty patients in each group will have blood drawn to measure drug levels.
Progress: This protocol remains open to enrollment, with no patients enrolled.
155
Detail Summary Sheet
Date: 30 Sep 06 Number: 204064 Status: Ongoing
Title: SWOG S0230, Phase III Trial of LHRH Analog Administration During Chemotherapy to
Reduce Ovarian Failure Following Chemotherapy in Early Stage, Hormone- Receptor Negative
Breast Cancer
Principal Investigator: MAJ Jasmine T. Daniels, MC
Department: Medicine/Hematology & Oncology Facility: MAMC
Associate Investigator(s): MAJ Angela G. Mysliwiec, MC; LTC David E. McCune, MC; LTC
John B. Halligan, MC
Start - Completion: Funding: Periodic Review:
7/27/2004 - Apr 2009 SWOG via Henry M. Jackson Foundation 4/20/2006
Study Objective: (1) To compare the rate of premature ovarian failure at two years following
standard adjuvant chemotherapy with or without the addition of ovarian suppression with a
LHRH analog during chemotherapy in premenopausal women with early stage, hormone-receptor
negative breast cancer. (2) To compare rates of ovarian dysfunction at one year and two years
following standard adjuvant chemotherapy with or without ovarian suppression and to evaluate
ovarian reserve in the two groups at one and two years. In addition, this study will describe
pregnancy and other fertility information in the two groups after treatment and during the five
year follow-up period.
Technical Approach: This is a randomized national phase III trial comparing standard adjuvant
chemotherapy with chemotherapy plus Goserelin in pre-menopausal women with Stage I, II or
IIIA Estrogen receptor negative and progesterone receptor negative breast cancer. Suppression of
ovarian function during chemotherapy with a LHRH analog has demonstrated high rates of
ovarian preservation in small studies. Outcome variables include the rate of amenorrhea at the
completion of chemotherapy, at one year and at two years following treatment. Serum levels of
FSH, estradiol and inhibin B will also be obtained at these same time points. Fertility information
to include the number of successful pregnancies and the number of miscarriages will be compared
at one, two and five years after treatment. National accrual is 416 patients over three years of
which an estimated 3 per year will be enrolled at MAMC.
Progress: This study remains open to enrollment, with no patients enrolled.
156
Detail Summary Sheet
Date: 30 Sep 06 Number: 206068
Status: Ongoing
Title: SWOG S0520: Phase II Study of PXD101 (NSC-726630) in Relapsed and Refractory
Aggressive B-Cell Lymphomas
Principal Investigator: MAJ Jasmine T. Daniels, MC
Department: Medicine/Hematology & Oncology
Facility: MAMC
Associate Investigator(s): MAJ Angela G. Mysliwiec, MC; LTC David E. McCune, MC
Start - Completion: Funding:
7/24/2006 - May 2011 SWOG via Henry M. Jackson Foundation
Periodic Review:
N/A
Study Objective: Primary objectives: (1) To evaluate response rate and toxicity in patients with
relapsed and refractory aggressive B-cell lymphoma treated with this regimen. (2) To estimate the
6-month progression-free survival rate in patients with relapsed and refractory aggressive B-cell
lymphoma with single agent PXD101 therapy. Correlative study objectives: (1) to assay the MHC
Class II proteins (HLA-DR, DP, DQ), TUNEL and CD8 infiltration status by
immunohistochemistry on paired pre- and post-treatment tumor samples for 20 patients on the
enrolled, (2) to measure CIITA and HLA-DR mRNA expression using quantitative RT-PCR, and to
explore in a preliminary manner the associations of these markers and progression-free survival
and (3) to evaluate paired pre- and post-treatment peripheral blood mononuclear cells (PBMCs)
from patient for histone acetylation conducted on pre- and post-needle core biopsies.
Technical Approach: This is a Phase II, open label, multi-site study of PXD101 in relapsed and
refractory aggressive B-cell lymphoma. This study will enroll a total of 60 subjects (up to 3 at
MAMC) with diffuse large, Burkitt's, Burkitt-like, primary mediastinal lymphoma. Patients will
receive PXD101 at a dose of 1,000 mg/m2, as a 30 minute IV infusion, on Days 1-5 of a 21 day
cycle. Nausea, vomiting, anemia, neutropenia and dehydration will be treated according to
institutional standards. Diarrhea will be treated with loperamide. Treatment will be given on
Days 1-5 of a 21 Day cycle. Physicals, laboratory tests and adverse event evaluation will be done
prior to each subsequent cycle. Disease assessment will be done after Cycle 3, and then every 4
cycles until progression is documented. Patients will be removed from treatment after disease
progression, symptomatic deterioration, unacceptable toxicity or completion of 2 years of
treatment. Off-treatment evaluation will include monitoring for disease progression and survival
for up to a total of 3 years. The primary goal of this study is to assess the response probability in
patients with relapsed or refractory aggressive B-cell lymphoma treated with PXD101. Secondary
endpoints will include toxicity, overall survival, time to treatment failure and time to progression.
It is assumed that this therapy will be of no further interested if the true response probability is
5% or less, and of interest if the true response probability is 20% or more. The study has a two-
stage design. If at least one of the first 20 patients responds, an additional 20 patients will be
enrolled.
Progress: This protocol is open to patient entry, with no patients enrolled during FY06.
157
Detail Summary Sheet
Date: 30 Sep 06 Number: 91094 Status: Ongoing
Title: SWOG S9007 (ECOG S9007), Cytogenetic Studies in Leukemia Patients
Principal Investigator: MAJ Jasmine T. Daniels, MC
Department: Medicine/Hematology & Oncology Facility: MAMC
Associate Investigator(s): MAJ Angela G. Mysliwiec, MC; LTC David E. McCune, MC; LTC
Tommy A. Brown, MC
Start - Completion: Funding: Periodic Review:
2/7/1992 - Indef SWOG via Henry M. Jackson Foundation 1/12/2006
Study Objective: (1) To estimate the frequencies and prognostic significance of cytogenetic
abnormalities in marrow or blood cells of leukemia patients prior to treatment on Southwest
Oncology Group protocols and at various times in the course of their treatment, (2) To estimate
correlations between the presence of cytogenetic features and of clinical, pathophsiological,
cellular, or molecular characteristics in these patients and (3) To provide quality control for all
Southwest Oncology Group cytogenetic data.
Technical Approach: This is a companion protocol for all Southwest Oncology Group leukemia
protocols. Bone marrow or peripheral blood specimens will be forwarded to a SWOG referral
cytogenetics laboratory (Oregon Health Sciences University, Portland, Oregon is the nearest to
Madigan Army Medical Center). The referral lab will return a cytogenetics report to MAMC.
Specimens will be collected as outlined in each individual leukemia protocol.
Progress: This protocol is the cytogenetic companion study to SWOG leukemia treatment protocol
SO 106. It remains open to enrollment with no subjects enrolled.
158
Detail Summary Sheet
Date: 30 Sep 06 Number: 99019
Status: Ongoing
Title: SWOG S9808: Long-Term Follow-Up Protocol: An Administrative Tool
Principal Investigator: MAJ Jasmine T. Daniels, MC
Department: Medicine/Hematology & Oncology
Facility: MAMC
Associate Investigator(s): MAJ Angela G. Mysliwiec, MC; LTC David E. McCune, MC; LTC
Tommy A. Brown, MC
Start - Completion: Funding:
10/20/1998 - Indef SWOG via Henry M. Jackson Foundation
Periodic Review:
10/10/2006
Study Objective: To relieve the burden on Institutional Review Boards at Southwest Oncology
Group Institutions for continuing review of protocols that are closed to patient registration, and on
which no patients are currently receiving protocol treatment.
Technical Approach: When a study has been closed to patient accrual and patients have
finished treatment, it still requires submission of data to the Southwest Oncology Group to report
survival and remission status and occurrence of adverse events. On an annual basis, the
Southwest Oncology Group Operations Office will notify the institutions as to which protocols are
eligible for transfer to the Long Term Follow-Up protocol by periodically revising the list of
applicable protocols. The institutional Principal Investigator or IRB will ultimately decide for the
local institution whether the protocol should be included in this protocol or continue to be reviewed
on its own. A report will be prepared and submitted for annual IRB review at individual
institutions. This report will include title and date closed to patient entry.
Progress: During FY06, the following protocols continued to have patients followed under this
long-term follow-up tool: 8516, 1 patient; 8794, 1 patient; 8809, 2 patients; 9008, 1 patient; 9035, 1
patient; 9133, 2 patients; 9304, 1 patient; and 9349, 2 patients.
Protocols terminated during FY06 and patients added to this administrative tool are: 8814, 3
patients; 8897, 6 patients; and 9313 1 patient.
Protocols that no longer required follow-up data during FY06: 8294, 5 patients; 9003, 1 patient;
and 9415, 1 patient.
159
Detail Summary Sheet
Date: 30 Sep 06 Number: 205035
Status: Ongoing
Title: SWOG S9910 Leukemia Centralized Reference Laboratories and Tissue Repositories,
Ancillary
Principal Investigator: MAJ Jasmine T. Daniels, MC
Department: Medicine/Hematology & Oncology
Facility: MAMC
Associate Investigator(s): MAJ Angela G. Mysliwiec, MC; LTC David E. McCune, MC
Start - Completion: Funding:
3/18/2005 - Feb 2010 SWOG via Henry M. Jackson Foundation
Periodic Review:
1/4/2006
Study Objective: (1) To develop and apply laboratory assays for the rapid and precise diagnosis
of leukemia patients and identify biologic, genetic, and molecular parameters that distinguishes
different subtypes of human leukemia with differing responses to therapy. (2) To develop risk-
adapted' therapeutic approaches in which biologic, genetic, and molecular parameters are sued to
target individual patients to tailored therapeutic regimens, or, to randomize and stratify patients
to different treatment arms of a therapeutic trial. (3) To develop new automated and standardized
laboratory methods for the detection and monitoring of therapeutic responsiveness and minimal
residual disease in leukemia patients and develop new clinical approaches to employ such data in
therapeutic decision making and clinical trial design. (4) To maintain and expand tissue
repositories of highly characterized leukemia samples from uniformly treated Southwest oncology
Group patients to promote Intergroup and external fundamental scientific collaborations and to
perform continued critical prospective and retrospective correlative biologic studies. (5) To utilize
scientific information generated from Intergroup and collaborative studies to assist the leukemia
committee in the development of new and more effective treatment regimens.
Technical Approach: The Southwest Oncology Group repositories are banks of extremely
valuable leukemia samples which are made available to researchers who are studying various
biological parameters and therapeutic diseases.
Progress: This protocol remains open to enrollment, with no patients enrolled.
160
Detail Summary Sheet
Date: 30 Sep 06 Number: 200084 Status: Ongoing
Title: SWOG S9921: Adjuvant Androgen Deprivation versus Mitoxantrone plus Prednisone plus
Androgen Deprivation in Selected High Risk Prostate Cancer Patients Following Radical
Prostatectomy, Phase III
Principal Investigator: MAJ Jasmine T. Daniels, MC
Department: Medicine/Hematology & Oncology Facility: MAMC
Associate Investigator(s): MAJ Angela G. Mysliwiec, MC; LTC David E. McCune, MC; LTC
Tommy A. Brown, MC
Start - Completion: Funding: Periodic Review:
9/26/2000 - Jan 2002 SWOG via Henry M. Jackson Foundation 5/23/2006
Study Objective: This study will evaluate overall survival using adjuvant systemic therapy in
high risk localized prostate cancer patients following radical prostatectomy. Disease-free survival
will also be evaluated. Patients will be randomized to one of the following two treatment arms: (A)
Casodex, + Zoladex, (B) Novantrone/Prednisone followed by Casodex, + Zoladex. This study will
also compare qualitative and quantitative toxicity between the two study arms.
Technical Approach: This study compares standard hormonal therapy after prostate cancer
surgery to standard therapy plus chemotherapy to determine the best way to prevent relapse.
Subjects will be randomized to receive either Treatment 1, Hormonal Therapy which consists of
Zoladex, subcutaneous injection once every 12 weeks for two years or Treatment 2, Hormonal
Therapy plus Mitoxantrone plus Prednisone which consists of Zoladex subcutaneous injection once
every 12 weeks for two years, Casodex taken orally once a day for two years, Mitoxantrone, IV
once every 21 days for 126 days (6 cycles) and Prednisone, taken orally twice a day for 126 days.
Following study completion, subjects will be followed every 6 months for two years to assess
response.
Progress: This protocol is open to patient entry, with thirteen patients enrolled to date. Five
patients continue to receive study treatment; the remaining eight patients continued to be followed
at MAMC during FY06.
161
Detail Summary Sheet
Date: 30 Sep 06 Number: 202074
Status: Ongoing
Title: SWOG S9925 Lung Cancer Specimen Repository Protocol, Ancillary
Principal Investigator: MAJ Jasmine T. Daniels, MC
Department: Medicine/Hematology & Oncology
Facility: MAMC
Associate Investigator(s): MAJ Angela G. Mysliwiec, MC; LTC David E. McCune, MC; LTC
Tommy A. Brown, MC
Start - Completion: Funding:
Periodic Review:
9/24/2002 - Nov 2005 SWOG via Henry M. Jackson Foundation
5/22/2006
Study Objective: (1) To establish a central lung cancer specimen repository to serve as a resource
for current and future scientific studies. (2) To utilize Southwest Oncology Group clinical database
to perform clinic pathologic correlation with the results of those studies. (3) To test new hypotheses
as they emerge.
Technical Approach: Patients enrolled into select other SWOG lung cancer studies will be asked
to consent to this study as well. Tissue samples will be obtained and stored.
Progress: This protocol is a companion study to other SWOG lung cancer treatment trials and
remains open to patient entry, with three patients enrolled at MAMC; all now deceased.
162
Detail Summary Sheet
Date: 30 Sep 06 Number: 204073 Status: Ongoing
Title: A Multicenter, Randomized, Phase III Study of Rituximab versus Iodine I 131
Tositumomab Therapeutic Regimen for Patients with Relapsed Follicular Non-Hodgkin's
Lymphoma, Protocol CCBX001-049
Principal Investigator: LTC David E. McCune, MC
Department: Medicine/Hematology & Oncology Facility: MAMC
Associate Investigator(s): MAJ Angela G. Mysliwiec, MC; MAJ Jasmine T. Daniels, MC; LTC
Maricela Contreras, MC; COL Marc G. Cote, MC; LTC Antonio G. Balingit, MC; Jane E. Besich-
Carter, BS, BCNP
Start - Completion: Funding: Periodic Review:
7/26/2004 - Jun 2016 Corixa Corporation via Henry M. Jackson 4/20/2006
Foundation
Study Objective: (1) To compare the event-free survival, as assessed by a Masked Independent
Randomized Radiographic and Oncologic Review (MIRROR) Panel, of patients treated with
rituximab to that of patients treated with the Iodine 1-131 Tositumomab therapeutic regimen in
patients who have had at least one, but no more than two, prior therapies for follicular non-
Hodgkin's lymphoma (NHL). (2) To compare confirmed response rates, durations of response, time
to next treatment, and progression-free survival of patients treated with rituximab to that of
patients treated with the Iodine 1-131 Tositumomab therapeutic regimen in patients who have had
at least one, but no more than two, prior therapies for follicular NHL, as assessed by a MIRROR
panel, to compare overall survival in these two treatment groups, and to assess and compare the
safety of rituximab and Iodine 1-131 Tositumomab when administered to this patient population.
(3) To summarize safety and efficacy outcomes during follow-up after subsequent therapy for NHL
for patients in both arms who receive additional therapy.
Technical Approach: This is a multicenter, randomized, Phase 3 trial to compare rituximab and
the Iodine I 131 Tositumomab therapeutic regimen in the treatment of subjects with follicular non-
Hodgkin's B-cell lymphoma. Randomization will be stratified by prior rituximab treatment, first
versus second relapse, and region, (US or outside the US). In Arm A, subjects will receive 375
mg/m2 of rituximab as an IV infusion once weekly for 4 weeks. In Arm B, subjects will undergo a
two phase treatment. In the dosimetric phase, subjects will receive an infusion of unlabeled
Tositumomab (450mg) immediately followed by an infusion of 5 mCi (0.18 GBq) of Iodine I 131
Tositumomab (35 mg.) Whole body gamma camera scans will be obtained 3 times after the
dosimetric dose. A patient-specific administered activity of Iodine I 131 Tositumomab will be
calculated to deliver the desired total body dose of radiation (65 or 75 cGy).
In the second phase (therapeutic dose), subjects in Arm B will receive an infusion of unlabeled
Tositumomab (450mg) immediately followed by infusion of the patient-specific activity of Iodine I
131-conjugated Tositumomab (35 mg.) Thyroid blockade will be implemented 24 hours prior to the
dosimetric dose and continued for 14 days following. Hematology and serum chemistry will be
measured for safety assessments weekly (hematology) and approximately monthly (chemistry)
through Week 13, then at scheduled study follow up visits. Approximately 506 subjects will be
randomized in the trial, and about 6 will participate at MAMC. The study will be conducted in the
Hematology and Oncology Clinic in collaboration with the Nuclear Medicine Service. Subject
accrual will continue for about 2 years. Subjects will be followed for response and safety
measurements at weeks 7 and 13 and every 3 months for the first and second year, every 6 months
for the third year, annually for the fourth and fifth years, then for long term follow up for survival,
safety, and additional therapy data through year ten. After subsequent NHL therapy, follow up
will assess tolerance of next anti-lymphoma therapy, development of NDS/AML, HAMA, or
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hypothyroidism, unexpected safety issues, and death.
The primary analysis is the intent to treat comparison of event-free survival between treatment
arms, which will be based on the MIRROR panel assessment of event-free survival. Secondary
analyses will include the comparison of response rates and complete response rates (confirmed)
and separate analyses will evaluate other responses, duration, time to next treatment, and overall
survival. Secondary and exploratory analyses will include a stratified log rank test adjusting for
stratification. Kaplan-Meier formula will be used to estimate duration curves and percentiles.
Estimates and confidence limits will be calculated by the product limit method and Greenwood's
formula for variance. Safety will be summarized within treatment arms and compared across
treatment arms.
Progress: This protocol remains open to enrollment with no patients screened or enrolled during
FY06.
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Detail Summary Sheet
Date: 30 Sep 06 Number: 205093 Status: Ongoing
Title: A Phase 3, Double-Blind, Placebo- Controlled Study of Maintenance Premetrexed plus Best
Supportive Care versus Best Supportive Care Immediately Following Induction Treatment for
Advanced Non-Small Cell Lung Cancer AND COMPANION STUDY Companion Translational
Research Protocol
Principal Investigator: LTC David E. McCune, MC
Department: Medicine/Hematology & Oncology
Facility: MAMC
Associate Investigator(s): MAJ Jasmine T. Daniels, MC; MAJ Angela G. Mysliwiec, MC
Start - Completion: Funding:
10/27/2005 - Aug 2010 Eli Lilly and Company via Henry M. Jackson
Foundation
Periodic Review:
7/20/2006
Study Objective: (1) To compare maintenance therapy with Premetrexed plus best supportive
care (BSC) versus placebo plus BSC, in terms of the overall survival time (OS) in patients with
Stage IIIB (with pleural effusion and/or positive supraclavicular lymph nodes) or IV NSCLC who
have not progressed during four cycles of platinum-based induction chemotherapy. (2) To compare
the following between the randomized treatment arms: Time to event efficacy endpoints:
Progression-free survival time (PFS), Time to objective progressive disease (TPD), Time to
worsening of symptoms (TWS), Objective tumor response rate, Adverse events, and Changes in
individual symptom scores and quality of life using the Lung Cancer Symptom Scale (LCSS).
Technical Approach: This is a phase 3, global, multicenter, randomized, double-blind, placebo-
controlled study to compare maintenance therapy with Premetrexed plus BSC versus placebo in
terms of overall survival time in patients with stage IIIB (with pleural effusion and/or positive
supraclavicular lymph nodes) or stage IV NSCLC who have not progressed during four cycles of
platinum-based induction chemotherapy. Eligible patients will be randomly assigned to receive
Premetrexed plus BSC or placebo plus BSC. Patients in both treatment arms will receive folic acid,
vitamin B12 supplements and dexamethasone. Each patient will undergo a treatment period and a
follow-up period. The treatment period consists of 21 day treatment cycles. Patients will receive
treatment (control or experimental) until objective disease progression. The follow-up period
begins when the patient discontinues study treatment. Patients are to be followed with a periodic
tumor response evaluation until objective disease progression. All patients will be followed until
death or study closure.
The study will apply technology to evaluate intratumoral gene expression, followed by protein
expression and DNA polymorphisms of key genes involved in the cellular transport, activation and
cytotoxic activity of Premetrexed. All subjects entered into the clinical study will be invited to
participate in the companion protocol. Samples will be shipped to the sponsor Eli Lilly and
Company and will be stored for a maximum of 3 years after the companion study is completed and
then the tissue samples will be destroyed.
Progress: This protocol remains open to enrollment with no subjects screened or consented during
FY06.
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Detail Summary Sheet
Date: 30 Sep 06 Number: 206014
Status: Ongoing
Title: A Phase I/II Trial of Zometa in Patients with Monoclonal Gammopathy of Undetermined
Significance (MGUS)
Principal Investigator: LTC David E. McCune, MC
Department: Medicine/Hematology & Oncology
Facility: MAMC
Associate Investigator(s): MAJ Jasmine T. Daniels, MC; MAJ Angela G. Mysliwiec, MC
Start - Completion: Funding:
6/6/2006 - July 2010 Oncotherapeutics via Henry M. Jackson
Foundation
Periodic Review:
10/16/2006
Study Objective: To determine the effect of zoledronic acid on bone mineral density (BMD) of
lumbar spine, utilizing dual energy x-ray absorptiometry (DEXA) scan, among patients with
MGUS with associated osteopenia/osteoporosis. The secondary objectives of this study are to:
determine the effect of zoledronic acid on skeletal fractures in MGUS patients with
osteopenia/osteoporosis, determine the effect of zoledronic acid on BMD of total hip, determine the
effect of zoledronic acid on serum M-protein levels, determine the proportion of patients treated
with zoledronic acid that develop multiple myeloma or other related malignancies, and determine
the safety of the use of zoledronic acid in the treatment of MGUS patients with
osteopenia/osteoporosis.
Technical Approach: This is an open label study designed to evaluate the efficacy and safety of
zoledronic acid in MGUS patients with osteopenia/osteoporosis. A screening visit will be conducted
within 14 days before baseline (baseline being prior to the administration of the first dose of study
drug). At this visit, a medical history will be obtained and a complete physical examination will be
performed including vital signs, weight, 12-lead electrocardiogram, and postero-anterior and
lateral chest x-rays. Pre-study disease assessment will be performed, including bone mineral
density (BMD) of lumbar spine, Karnofsky Performance Status (KPS), skeletal survey, bone
marrow aspirate and biopsy (patients will be required to have this procedure if bone marrow
aspirate and biopsy has never been performed to rule out the possibility of malignancy), serum and
urine protein electrophoreses. The bone marrow aspirate and biopsy will be evaluated for degree of
plasma cell involvement. Clinical laboratory tests including hematology, clinical chemistry
(including electrolytes, calcium, magnesium and random glucose), liver tests, urinalysis, and
serum pregnancy tests for women of child-bearing potential will also be performed at the
Screening visit. Patients who meet the eligibility requirements as assessed at the Screening visit
will be enrolled in the study. Zoledronic acid at 4 mg will be administered intravenously every 6
months over a period of 12 months. Patients are to attend a Final study visit. Procedures to be
conducted at this visit include a complete physical examination, adverse event assessment, vital
signs, Karnofsky performance status assessment and clinical chemistry.
Progress: This protocol opened to patient entry in June 2006; no subjects have been screened or
enrolled.
166
Detail Summary Sheet
Date: 30 Sep 06 Number: 205016 Status: Terminated
Title: A Phase II Multicenter, Randomized, Double-blind, Placebo-controlled Dose-Ranging,
Parallel Group Study of the Safety and Efficacy of the Oral Neurokinin- 1 Receptor Antagonist,
GW679769, When Administered as 50mg, lOOmg, and 150mg Oral Tablets in Combination with
Ondansetron Hydrochloride and Dexamethasone for the Prevention of Chemotherapy- Induced
Nausea and Vomiting in Cancer Subjects Receiving Moderately Emetogenic Chemotherapy
Principal Investigator: LTC David E. McCune, MC
Department: Medicine/Hematology & Oncology
Facility: MAMC
Associate Investigator(s): MAJ Angela G. Mysliwiec, MC; MAJ Jasmine T. Daniels, MC
Start - Completion: Funding:
2/28/2005 - Jan 2007 GlaxoSmithKline via Henry M. Jackson
Foundation
Periodic Review:
11/3/2006
Study Objective: Primary objectives: (1) To determine the optimal dose of oral GW679769 when
administered in combination with ondansetron hydrochloride and dexamethasone for the
prevention of vomiting during the first 120 hours in subjects receiving their first cycle of
moderately emetogenic chemotherapy. (2) To determine the optimal dose of oral GW679769 when
administered in combination with ondansetron hydrochloride and dexamethasone for the
prevention of nausea during the first 120 hours in subjects receiving their first cycle of moderately
emetogenic chemotherapy.
Secondary objectives: (1) To determine the safety of oral GW679769 at various dose levels
when administered in combination with ondansetron hydrochloride and dexamethasone in subjects
receiving their first cycle of moderately emetogenic chemotherapy. (2) To quantify the impact on
daily life activities of oral GW679769 when administered in combination with ondansetron
hydrochloride and dexamethasone during the first 120 hours in subjects receiving their first dose
of moderately emetogenic chemotherapy. (3) To evaluate the population pharmacokinetics and
pharmaco-dynamics (PK/PD) of oral GW679769 and its active metabolites when administered in
combination with ondansetron hydrochloride and dexamethasone in subjects receiving their first
cycle of moderately emetogenic chemotherapy.
Technical Approach: This trial is a double-blind, randomized, placebo-controlled, dose-ranging,
parallel group study of the safety and efficacy of the oral neurokinin- 1 receptor antagonist
GW679769. At MAMC, the study will be conducted by the Hematology/ Oncology service with up to
20 subjects enrolled out of a total of 708 subjects in the study overall. Subjects scheduled to begin
chemotherapy with a moderately emetogenic regimen will be consented and screened in the
oncology service. On day 1 prior to the first chemotherapy cycle, subjects will be administered
ondansetron hydrochloride (8mg or 16 mg), intravenous Dexamethasone (8mg) and an oral dose of
GW679769 investigational produce (active or placebo). Subjects in groups 1, 2, 3, 4, or 5 will
receive a second dose of oral ondansetron hydrochloride 8 hours following the initial dose.
Subsequent dose or doses of ondansetron hydrochloride will be administered bid on days 2 and 3.
For treatment group 6, the initial daily dose of ondansetron hydrochloride for days 1, 2 and 3 will
be 16mg, followed by a second daily dose of ondansetron hydrochloride placebo. For study groups 1,
2, 3, 4 and 6, GW679769 will be administered once daily on study days 2 and 3 at the same dose as
day 1. Subjects randomized to group 5 will receive a single active dose of GW679769 on day 1, and
receive a single daily dose of GW679769 placebo on days 2 and 3. For study subjects who are
receiving a taxane based therapy, Dexamethasone will not be given according to protocol, but will
be given according to MAMC standard procedure for that specific chemotherapy regimen.
Progress: This protocol closed to enrollment with no subjects enrolled at MAMC. A final site close
out visit was conducted in November 2006.
167
Detail Summary Sheet
Date: 30 Sep 06 Number: 205087 Status: Suspended
Title: A Phase II, Open Label, Multi-center Study of EP2101 Therapeutic Vaccine in Patients
with Stage Illb, Stage IV, or Recurrent Non-Small Cell Lung Cancer (NSCLC)
Principal Investigator: LTC David E. McCune, MC
Department: Medicine/Hematology & Oncology Facility: MAMC
Associate Investigator(s): MAJ Jasmine T. Daniels, MC; MAJ Angela G. Mysliwiec, MC; LTC
Mark L. Nelson, MC
Start - Completion: Funding: Periodic Review:
9/21/2005 - Jul 2010 Epimmune via Henry M. Jackson Foundation 6/27/2006
Study Objective: (1) To compare the overall survival of patients with stage Illb, IV, or recurrent
non-small cell lung cancer treated with EP2101 therapeutic vaccine to a concurrent non-HLA-A2
observation group and historical controls. (2) To evaluate the safety of EP2101 therapeutic vaccine.
Secondary: (1) To determine progression-free survival time in patients treated with EP2101
therapeutic vaccine. (2) To determine the frequency, magnitude, and breadth of cytotoxic and
helper T-Cell responses to EP2101 vaccine epitopes.
Technical Approach: At MAMC, the study will be conducted by the Hematology/Oncology
Service with up to 12 MAMC subjects expected to enroll, about 6 in the vaccine group and 6 in the
observational group. A total of 168 subjects may be enrolled in the study overall. Patients who
qualify will be consented to have their HLA type tested. Patients who do not qualify for the vaccine
portion of the trial will be consented for the observational arm if they are interested. They will
have a baseline medical history and physical, QOL, laboratory testing including CBC, chemistry,
urinalysis and pregnancy test if applicable. Observational patients will be seen at Wk9, Wkl8,
Wk22, Mo6, Mo7, Mo9, Mol2, then every three months for years 2 and 3, and annually for years 4
and 5. Visits will include QOL, con meds, disease progression and survival status.
Patients who qualify for the vaccine arm of the trial (HLA type A2) will be consented and have the
following pre-study assessment: complete medical history and physical exam, ECOG status
performance, concomitant medications, laboratory testing including CBC, chemistry, ANA
(autoimmunity), urinalysis and pregnancy testing if applicable, ophthalmic exam, disease
assessment by CT or MRI scan, and Quality of Life (QOL) questionnaire. These patients will also
be referred out to another facility to have leukapheresis performed, or have a 215 ml blood sample
collected using a pediatric blood unit collection bag, to submit for immunogenicity and helper T-cell
assays. Patients will receive the study vaccine once every three weeks for 6 cycles, for a total of 18
weeks of treatment. Patients will be monitored by the research nurse in the clinic for observation
for 60 minutes after each vaccine, to assess for adverse events. At Wk 9 and 18, patients will have
disease assessments done by CT or MRI, QOL, and laboratory tests including urinalysis, ANA, and
blood collected for immunogenicity and helper T-cell assays. After treatment, patients will be
followed at WK 22 and Mo7 for physical exam and ECOG score, laboratory tests including CBC
and chemistry, adverse event and con med assessment and survival status. In addition, at Mo6,
Mo 9 and Mol2, assessments will include disease progression monitored with CT or MRI, QOL,
and laboratory tests including urinalysis, ANA, and blood collected for immunogenicity and helper
T-cell assays. Long term follow up assessment of survival status will be scheduled every three
months for years 2 and 3, then annually for years 4 and 5.
Toxicities will be graded at each study visit according to the National Cancer Institute (NCI)
Common Toxicity Criteria (CTC) Version 3.0. Patients will be withdrawn from treatment for >
Grade 2 toxicity of allergic reaction, hypersensitivity, autoimmune reaction or vasculitis, or for >
168
Grade 3 cytokine-like release reaction or local skin reaction. The study will be placed on hold for
safety review if toxicities exceed the safety criteria outlined on Pg 37 of the protocol.
Progress: This protocol closed to enrollment with three subjects consented and enrolled. One
subject had disease progression and is no longer on the treatment arm; two subjects remain on
treatment.
169
Detail Summary Sheet
Date: 30 Sep 06 Number: 205070
Status: Ongoing
Title: A Phase II Study Using Alemtuzumab Combined with Fludarabine for the Treatment of
Relapsed/Refractory B-cell Chronic Lymphocytic Leukemia (B-CLL)
Principal Investigator: LTC David E. McCune, MC
Department: Medicine/Hematology & Oncology
Facility: MAMC
Associate Investigator(s): MAJ Jasmine T. Daniels, MC; MAJ Angela G. Mysliwiec, MC
Start - Completion: Funding:
7/13/2005 - Jun 2010 Berlex Laboratories via Henry M. Jackson
Foundation
Periodic Review:
4/20/2006
Study Objective: The primary objective is to evaluate complete response rate in patients
receiving combination treatment with Alemtuzumab and fludarabine. The secondary objectives are
to evaluate over all response rate, survival at 1 year, time to progression, duration of response,
adverse event profile, minimal residual disease and lymphocyte and lymphocyte subset recovery.
Technical Approach: This is a Phase II, open label trial of the combination of alemtuzumab and
fludarabine for the treatment of relapsed/refractory B-cell chronic lymphocytic leukemia. This
study will evaluate the response rate, survival, time to progression, duration of response
lymphocyte subset recovery and safety profile of the combination of subcutaneous alemtuzumab
and fludarabine. Patients will receive four 28-day cycles of treatment with alemtuzumab 30 mg
subcutaneously followed by 25mg/m2 IV of fludarabine, daily on days 1 through 5. At the end of 4
cycles, patients will have an interim assessment to determine response to treatment. This will
include radiographs as needed and a bone marrow biopsy. Minimal residual disease assessment
will be performed on the marrow samples. Patients who have respond or have stable disease will
receive two additional cycles of chemo as in Cycles 1-4. After treatment is completed, subjects will
be followed up every 6 months for disease assessment, CMV, and flow cytometry for lymphocyte
subset analysis to be done monthly until CD4 and CD8 T cell counts recover to >200 cells/uL.
All patients will be prescribed Bactrim for PCP prophylaxis and famcyclovir for HSV prophylaxis
starting with Day 1, and continuing for at least 2 months after treatment, or until CD 4 counts are
>200 cells/ uL. Patients will be monitored for CMV status throughout the study and for 6 months
after treatment. If patients become CMV positive they will receive appropriate anti- CMV therapy
and may have study drug delayed until CMV treatment is complete. Growth factors may be used
at the discretion of the investigator for Grade 3 or 4 neutropenia, however TPO and pegfilgrastim
will not be allowed. Toxicities will be graded at each study visit according to the National Cancer
Institute (NCI) Common Toxicity Criteria (CTC) Version 3.0 Safety will be assesses through
physical examinations and laboratory assessments at each study visit.
Progress: This protocol was closed to enrollment at MAMC due to a lack in screening and
enrollment activity.
170
Detail Summary Sheet
Date: 30 Sep 06 Number: 206126 Status: Ongoing
Title: A Phase II Trial of Imatinib (Gleevec) Plus Gemcitabine In Patients With Ovarian
Carcinoma Who Have Failed At Least One Prior Chemotherapy
Principal Investigator: LTC David E. McCune, MC
Department: Medicine/Hematology & Oncology Facility: MAMC
Associate Investigator(s): MAJ Angela G. Mysliwiec, MC; MAJ Jasmine T. Daniels, MC; MAJ
Richard D. Reed, MC
Start - Completion: Funding: Periodic Review:
11/20/2006 - Oct 2011 ACOSOG via Henry M. Jackson Foundation N/A
Study Objective: (1) To evaluate the cytostatic, anti-tumor activity of the combination of
Gleevec™ (Imatinib Mesylate) and gemcitabine via progression-free survival for at least six
months in subjects with recurrent or persistent epithelial ovarian or primary peritoneal
carcinoma. (2) To assess the tumor response rates using modified SWOG criteria to the
combination of Gleevec™ (Imatinib Mesylate) and gemcitabine in subjects with relapsed ovarian
cancer who have failed at least one prior chemotherapy treatment. (3) To determine the safety and
tolerability via frequency and severity of adverse effects of combination Gleevec™ and gemcitabine
in this cohort of subjects as assessed by CTC. (4) To determine the distribution of the overall
survival. (5) To estimate the clinical response rate (partial and complete response as defined under
the modified SWOG criteria). (6) To assess the effects of prognostic variables: initial performance
status, platinum sensitivity, and mucinous (or clear cell) histology on progression-free survival
overall.
Technical Approach: This is a Phase II, single arm, open label treatment study to evaluate the
tumor response rate to the combination of Gleevec and Gemcitabine for treatment of women who
have failed at least one prior chemotherapy regimen containing platinum. 60 subjects are expected
to enroll to achieve a goal of 56 evaluable subjects, with 20 subjects expected to enroll at MAMC.
Women will be recruited during regular visits to the Oncology Clinic; those appearing eligible will
be consented and screened. Those who qualify will be given a combination of oral Gleevec and IV
Gemcitabine, over a 21 day cycle, for as long as they respond and are able to tolerate the
combination. Subjects experiencing side effects may receive supportive care with growth factors or
antiemetics as appropriate or have their dose modified per protocol. Subjects will be followed after
each cycle by physical exams, laboratory assessments including CA-125 tumor marker, and by
review of adverse events and cancer-related symptoms. Tumor assessments will be done every
other cycle by CT or MRI. Subjects removed from treatment will be followed every three months
by clinic visit or phone contact for up to five years to determine time to progression and survival
rates.
Progress: This greater than minimal risk protocol received initial approval with stipulations
during the convened IRB meeting on 26 September 2006.
171
Detail Summary Sheet
Date: 30 Sep 06 Number: 204114
Status: Ongoing
Title: A Phase II Trial of Weekly Docetaxel plus Every 3-Week Carboplatin
Stage IIIB/IV Non-small Cell Lung Cancer, Protocol GIA 12156
in Patients with
Principal Investigator: LTC David E. McCune, MC
Department: Medicine/Hematology & Oncology
Facility: MAMC
Associate Investigator(s): MAJ Angela G. Mysliwiec, MC; MAJ Jasmine T. Daniels, MC
Start - Completion: Funding:
10/27/2004 - Nov 2007 Aventis Pharmaceuticals, Inc. via Henry M.
Jackson Foundation
Periodic Review:
8/29/2006
Study Objective: Primary Objective is to determine overall response rate for patients with
advanced non-small cell lung cancer treated with weekly docetaxel 35 mg/m2 on days 1 and 8 plus
carboplatin (AUC 6) on day 1 every 21 days. Secondary Objectives are to determine the 1-year
survival rate, the median overall survival rate, and to evaluate the safety and toxicity associated
with this regimen.
Technical Approach: This trial is a two- stage, phase II study of weekly docetaxel 35 mg/m2
infused on days 1 and 8 plus carboplatin (AUC 6) on day 1 only, repeated every 21 days (cycle) in
patients with stage IIIB or IV advanced non small cell lung cancer who have not received prior
chemotherapy. 4-6 MAMC subjects are expected to be enrolled. A total of 29 patients may be
enrolled in the study overall. Physical examination and history, baseline tumor assessments,
ECOG performance status, CBC, serum chemistry, EKG, and serum HCG as appropriate, will be
evaluated prior to study treatment. A minimum of two courses of treatment will be given unless
there is progression of disease or significant adverse reactions occur. Patients will be monitored
after every two cycles (6 weeks) for tumor response using standard radiographic imaging.
Objective response will be evaluated using the RECIST criteria (Response Evaluation Criteria In
Solid Tumors). Clinical and laboratory toxicities will be assessed and graded according to the NCI
Common Toxicity Criteria, version 2.0. Appropriate supportive care treatment will be
administered. Chemotherapy dose adjustments will be made based on the organ system exhibiting
the greatest degree of toxicity. Eligible patients will be treated for 2 additional cycles after best
documented tumor response. All patients will be followed after treatment at defined intervals for
survival data.
The primary endpoint of this study is overall response rate (complete response plus partial
response). Ten patients will be enrolled into the first stage. If at least 1 patient responds, 19
additional patients will be enrolled into the second stage of the study. If at least 5 of 29 evaluable
patients exhibit an objective response at the end of the second stage, the conclusion will be that
this regimen is worthy of further study. Secondary endpoints will be reported for the 1-year
survival rate, the median overall survival rate, evaluations of safety and toxicity associated with
this regimen. The primary efficacy analysis will be conducted on all patients who receive the study
drug. Objective tumor response rate along with exact 95% binomial confidence intervals will be
calculated. Time-to-event outcomes including 1-year survival, time to disease progression, and
duration of response will be estimated using the Kaplan- Meier product limit method. Median and
quartile estimates for each time-to-event outcome will be obtained from the Kaplan-Meier
estimates.
Progress: This protocol closed to enrollment with one subject enrolled who remains in follow-up
for survival information only. There are no unreported serious adverse events at the time of this
report.
172
Detail Summary Sheet
Date: 30 Sep 06 Number: 204006 Status: Terminated
Title: A Phase III, Randomized, Double-blinded Efficacy and Safety Study of Three Doses of
TAS-108 Administrated Orally in Postmenopausal Patients with Locally Advanced or Locally
Recurrent Inoperable or Progressive Metastatic Breast Carcinoma Lollowing Standard Lirst
Line Endocrine Therapy, Protocol Number TAS 108-0004
Principal Investigator: LTC David E. McCune, MC
Department: Medicine/Hematology & Oncology
Facility: MAMC
Associate Investigator(s): MAJ Angela G. Mysliwiec, MC; MAJ Jasmine T. Daniels, MC; M.
Rick Rutledge, MS
Start - Completion: Funding:
1/20/2004 - Jan 2006 Taiho Pharmaceutical Co., Ltd. via Henry M.
Jackson Foundation
Periodic Review:
11/22/2005
Study Objective: (1) To determine the efficacy of TAS-108 administered orally once daily at 40
mg, 80 mg, and 120 mg in postmenopausal patients with locally advanced or locally recurrent
inoperable or progressive metastatic ER/PgR positive breast carcinoma who have previously
responded to a standard first line endocrine therapy. (2) To evaluate the safety of TAS-108
administered on this schedule. (3) To investigate the comparative concentrations of TAS-108 and
its metabolite in tumor tissue and blood at steady-state. (4) To determine the time to progression
of TAS-108 administered on this schedule.
Technical Approach: This is a phase II, randomized, double-blinded study of TAS-108
administered orally once daily at 40 mg, 80 mg, or 120 mg to be carried out at multiple study sites.
The statistical calculation of the sample size will be based on a single arm study design and the
study will use this same number for each dose group. It is exactly the same as three identical
studies, using 40 mg, 80 mg, and 120 mg to be conducted at the same study sites at the same time.
The efficacy and safety results from each dose group will only be evaluated independently and
clinically, but not compared biostatistically. Patients will be enrolled to the 40 mg, 80 mg, and 120
mg dose levels randomly until the first stage number is met for each dose group. Depending on the
randomization schedule, the enrollment completion for each group may be far apart. The
enrollment will be put on hold for each respective dose group until the data to be evaluated meets
the preset criterion to proceed to the second stage. Since each dose group will be evaluated
separately and independently, the time point of meeting the preset criteria and allowing patients
to proceed into the second stage of the study will most likely be different for the three dose groups.
When the enrollment into the second stage of the study for each dose group is completed, analysis
for each group will be performed independently according to the analysis plan. In this study, one
course equals 28 days of treatment. Patients will receive study treatment until (a) there is
evidence of disease progression or (b) the patient develops unacceptable toxicity to TAS-108 or (c)
the patient withdraws informed consent.
Progress: This protocol was terminated by the PI in July 2006, with no subjects enrolled. Only
one patient had met the appropriate inclusion criteria, but she decided not to participate in the
study.
173
Detail Summary Sheet
Date: 30 Sep 06 Number: 204044 Status: Ongoing
Title: A Phase III Study of Delayed vs. Immediate Second-line Therapy with Docetaxel after
Gemcitabine + Carboplatin in Advanced Non- Small Cell Lung Cancer, Protocol Number B9E-
US-S245
Principal Investigator: LTC David E. McCune, MC
Department: Medicine/Hematology & Oncology
Facility: MAMC
Associate Investigator(s): MAJ Angela G. Mysliwiec, MC; MAJ Jasmine T. Daniels, MC
Start - Completion: Funding:
4/1/2004 - Apr 2007 SWOG via Henry M. Jackson Foundation
Periodic Review:
1/24/2006
Study Objective: Primary Objective is to test the value in terms of overall survival of immediate
sequential therapy with docetaxel compared to traditional second-line therapy with docetaxel at
the time of progression after standard Carboplatin and Gemcitabine in patients with stage Illb
and IV non-small cell lung cancer. Secondary Objectives: (1) to assess the response rate and time
to disease progression, (2) to compare toxicity in these two groups and (3) to compare quality of life
using the LCSS patient scale.
Technical Approach: This is a multicenter open-label randomized phase III trial to evaluate the
respective response rates, time to disease progression, survival time, toxicity, and quality of life of
immediate sequential therapy with docetaxel compared to traditional second-line therapy with
docetaxel at the time of disease progression, after standard Carboplatin and gemcitabine in
subjects with stage Illb and IV non- small cell lung cancer (NSCLC). Up to 5 MAMC subjects may
participate, with 550 subjects in the overall study. Duration of individual participation will be up
to 36 months. The study will enroll chemotherapy-naive subjects whose NSCLC is advanced at
diagnosis or has recurred or progressed following surgical treatment and/or radiation therapy, and
who meet additional eligibility criteria.
Following screening, eligible subjects will receive the first phase of treatment with gemcitabine
and Carboplatin chemotherapy on Day 1 and Day 8 every 21 days, followed by one week of rest, for
four cycles. Safety and response will be monitored. Disease restaging will be done at the end of
first phase treatment. Subjects with complete or partial response or stable disease after initial
therapy will be rescreened and eligible subjects will be randomized (1:1) to the second phase
treatment with immediate or delayed docetaxel. Subjects found to have progressive disease after
initial therapy or who discontinue prior to completion of 4 cycles will be followed for survival data.
Subjects randomized to delayed therapy will be monitored every three weeks prior to treatment.
Radiological imaging of tumor sites will be performed every 3 months or as clinically indicated.
With evidence of disease progression, subjects begin treatment with docetaxel. Subjects
randomized to receive immediate sequential docetaxel and subjects initiating traditional
treatment after progression will receive docetaxel on Day 1 every 3 weeks for a maximum of 6
cycles. Response and safety will be monitored. Subjects who complete the protocol or who
discontinue study chemotherapy early will be followed at protocol intervals until progression or
death. The primary endpoint is survival and will be measured from time of randomization to date
of death for all randomized subjects. Secondary endpoints of response rates, time to progression,
toxicity, and LCSS will be compared between regimens. An independent Data Safety Monitoring
Board will assess safety at the time of formal interim analysis, planned when 50% of subjects in
each docetaxel treatment arm have 1) died, 2) are lost to follow up prior to 24 months, or 3) have
been followed up for at least 24 months.
Progress: This protocol closed to enrollment with seven subjects consented. Five subjects are
deceased due to non-study related deaths and two patients continued to be followed during FY06.
174
Detail Summary Sheet
Date: 30 Sep 06 Number: 204096 Status: Completed
Title: A Randomized, Open-Label Study of PROCRIT® (Epoetin Alfa) Initiated at 40,000 Units
Every Week Versus 80,000 Units Every Two Weeks In Anemic Patients With Cancer Receiving
Chemotherapy, Protocol PR03-27-064
Principal Investigator: LTC David E. McCune, MC
Department: Medicine/Hematology & Oncology
Facility: MAMC
Associate Investigator(s): MAJ Angela G. Mysliwiec, MC; MAJ Jasmine T. Daniels, MC
Start - Completion: Funding:
9/15/2004 - Sep 2006 OrthoBiotech via Henry M. Jackson
Foundation
Periodic Review:
6/28/2005
Study Objective: Primary Objective: To compare end of study hemoglobin (Hb) levels of subjects
receiving epoetin alfa (PROCRIT®) 40,000 units administered subcutaneously once every week
with those receiving 80,000 units every two weeks, in anemic patients with cancer diagnosis and
receiving chemotherapy. Secondary Objectives: To assess Hb response, time to Hb response,
transfusion requirements, and safety of the two dose regimens.
Technical Approach: This is a randomized, open-label, multi-center trial that will compare
efficacy and safety of two dose regimens of Procrit® (Epoetin Alfa), 40,000 units administered
subcutaneously once every week with 80,000 units every two weeks, in anemic patients with non-
myeloid cancer diagnosis and receiving chemotherapy. 280 patients who meet all inclusion and
exclusion criteria will be enrolled and randomized at approximately 75 study centers to one of the
two treatment groups in a 1:1 ratio. The enrollment phase is expected to last 15 months. All
patients will be followed weekly until two weeks after the last dose of Epoetin Alfa, or up to a
maximum of 13 weeks on study (12 weeks of study drug). The starting doses may be adjusted per
protocol based on Hb response. If chemotherapy is completed before week 12, one final dose of
Epoetin Alfa will be administered on the assigned schedule at the end of the final cycle of
chemotherapy. Unless there is a contraindication, all patients will receive iron supplementation
(ferrous sulfate 325mg by mouth daily or an equivalent). Transfusions may occur as needed for
patient care. At MAMC, a hemoglobin value of less than 8.0 g/dL or a clinical judgment based on
symptoms will be the trigger event for blood transfusion. Subjects will be monitored weekly
during treatment and at study completion for blood pressure, hematologic response (hemoglobin
and hematocrit), adverse events, concomitant medications and transfusions. Physical exam with
vital signs, ECOG Performance Status, and laboratory testing as completed at screening will be
repeated at the end of study. The primary efficacy endpoint is end of study Hb, which will be
analyzed for the per-protocol and intent to treat populations. Safety analyses will describe adverse
events, laboratory values, physical exam, vital signs and ECOG status and will include all
randomized subjects receiving at least one dose of study medication.
Progress: This protocol closed to enrollment 16 May 05, and closed as a study site 22 November
2006, with eight subjects screened, two screen failures, six enrolled, four completed the study, one
was removed when relocated, and one subject removed for what was thought to be a thrombosis,
which turned out not to be so and was not reported as an event. No internal serious adverse events
were reports.
175
Detail Summary Sheet
Date: 30 Sep 06 Number: 202083 Status: Ongoing
Title: A Randomized Phase III Trial of Gemzar versus Doxil with Crossover Treatment Option
for Patients with Platinum-Resistant Ovarian, Fallopian Tube or Primary Peritoneal Cancer
Undergoing Second or Third-Line Chemotherapy, Protocol Number: B9E-US-S301
Principal Investigator: LTC David E. McCune, MC
Department: Medicine/Hematology & Oncology
Facility: MAMC
Associate Investigator(s): MAJ Angela G. Mysliwiec, MC; MAJ Jasmine T. Daniels, MC
Start - Completion: Funding:
8/14/2002 - Jul 2005 Lilly via Henry M. Jackson Foundation
Periodic Review:
5/22/2006
Study Objective: (1) To compare progression free survival in patients with platinum-refractory
epithelial ovarian, Fallopian tube, or primary peritoneal carcinoma who have failed two or less
prior regimens of chemotherapy that are treated with Doxil or Gemzar. (2) To compare response
rate, duration of response, time to treatment failure, survival, and quality of life in patients with
platinum-refractory epithelial ovarian, Fallopian tube, or primary peritoneal carcinoma who have
failed two or less prior regimens of chemotherapy who are treated with Doxil or Gemzar.
Technical Approach: At MAMC there are expected to be 5-10 patients enrolled during
approximately one year.
Patient screening will include written informed consent, medical history and demographics, tumor
assessment by exam or imaging, FACT-0 questionnaire, Zubrod Performance Status, LVEF,
chemistry and hematology, CA-125 tumor marker, contraceptive status and serum pregnancy test.
Patients on the Doxil arm will be treated with 50 mg/m2 on Day 1 of each 28 day cycle. Treatment
will continue for two cycles after a complete response, or until a cumulative maximum dose of 500
mg/m2 has been given. Patients on the Gemzar arm will be treated with 1000mg/m2 on Days 1
and 8 of a 21 day cycle. Treatment will continue for up to two cycles after complete response is
attained. For patients with stable disease there is no maximum number of Gemzar cycles. Patients
who have progressive disease may cross over to the other treatment arm if they are eligible.
Patients will be monitored every cycle for toxicities, chemistry, hematology, performance status
and CA-125 tumor staging. Dose adjustments will be made based on NCI toxicity criteria. FACT-
O Quality of Life questionnaire will be administered every other cycle, and tumor assessment
imaging will be performed every 12 weeks. Primary efficacy will be evaluated using Kaplan-Meier
techniques. Secondary efficacy analysis will be conducted on response rate, duration of response,
time to treatment failure, survival and quality of life. Response rates from the two treatment
arms will be compared using Fisher's Exact test. Summaries on toxicity parameters will be
provided.
Progress: This protocol closed to patient entry in May 2004, with four patients enrolled. Two
patients are deceased and two continued to be followed at MAMC during FY06. No patients are
receiving treatment. The protocol remains ongoing pending closeout of the database by the study
sponsor.
176
Detail Summary Sheet
Date: 30 Sep 06 Number: 204107 Status: Suspended
Title: CTSU ACOSOG-Z9001, A Phase III Randomized Double-blind Study of Adjuvant STI571
(Gleevec™) Versus Placebo in Patients Following the Resection of Primary Gastrointestinal
Stromal Tumor (GIST)
Principal Investigator: LTC David E. McCune, MC
Department: Medicine/Hematology & Oncology
Facility: MAMC
Associate Investigator(s): MAJ Angela G. Mysliwiec, MC; MAJ Jasmine T. Daniels, MC
Start - Completion: Funding:
11/1/2004 - Aug 2008 ACOSOG via Henry M. Jackson Foundation
Periodic Review:
12/12/2006
Study Objective: Primary Objective: To ascertain whether patients with resected primary GIST
who are randomized to the ST1571 Arm have longer recurrence-free survival as compared to the
patients randomized to the Placebo Arm. Secondary Objectives: (1) To ascertain whether patients
with resected primary GIST who are randomized to the STI571 Arm have longer survival as
compared to the patients randomized to the Placebo Arm. (2) To obtain from patients with GIST:
tumor tissue (before therapy with ST1571 and if the patient develops recurrence), blood specimens
(before therapy with STI571), and serum specimens (before therapy with ST1571, after completing
therapy with ST1571, and if the patient develops recurrence) for scientific correlative analyses. (3)
To assess the safety/efficacy of oral ST1571 therapy in the adjuvant setting.
Technical Approach: Patients will be randomized into one of two groups; four lOOmg capsules
for a total of 400mg of the experimental drug or placebo by mouth every day for 1 year. Weight
should be measured at home two times per week and the physician called if there is a weight
change by more than 4 pounds from the weight taken at the last clinic visit. Patients will have a
physical exam before the start of drug or placebo and then seen in the clinic weekly the first 2
weeks, at weeks 4, 6 and 8, at 3, 4, 5 and 6 months, every 3 months until year 2, every 6 months
until year 5 and then every year until death.
Tumor tissue will be sent to a central pathologist to confirm the diagnosis of GIST and if it has a
protein called Kit, as the presence of this protein is required for the Gleevec to work. If the tissue
sample results show that the tumor is not GIST or if the Kit protein is not there, the study drug
will be stopped and patients will have a physical examination and a blood test about 30 days after
the study drug is stopped. These patients will continue to be contacted by phone every 3 months
for 1 year, every 6 months for 3 years, and then every year until death.
Progress: This protocol remains open to enrollment, with one subject enrolled and remained on
active treatment during FY06.
177
Detail Summary Sheet
Date: 30 Sep 06 Number: 202114 Status: Ongoing
Title: CTSU CALGB 40101, Cyclophosphamide and Doxorubicin (CA) (4 VS 6 Cycles) versus
Paclitaxel (4 VS 6 Cycles) as Adjuvant Therapy for Women with 0-3 Positive Axillary Lymph
Nodes: A 2X2 Factorial Phase III Randomized Study
Principal Investigator: LTC David E. McCune, MC
Department: Medicine/Hematology & Oncology Facility: MAMC
Associate Investigator(s): MAJ Angela G. Mysliwiec, MC; MAJ Jasmine T. Daniels, MC; LTC
Tommy A. Brown, MC
Start - Completion: Funding: Periodic Review:
11/14/2002 - Oct 2005 SWOG via Henry M. Jackson Foundation 8/22/2006
Study Objective: Primary Objectives: (1) To determine the equivalence of paclitaxel given every
two weeks with CA given every two weeks as adjuvant therapy for women with 0-3 positive
axillary lymph nodes, for disease free survival. (2) To determine if longer therapy, 12 weeks, is
superior to shorter therapy, 8 weeks, of either CA or paclitaxel for disease-free survival for women
with primary breast cancer with 0-3 positive axillary lymph nodes.
Secondary Objectives: (1) To determine the equivalence of paclitaxel given every two weeks with
CA given every two weeks, and the potential superiority of longer vs. shorter therapy, in relation
to overall survival, local control (regardless of metastatic status) and time to distant metastases
(regardless of local recurrence status (2) Compare toxicities of short and long course CA and
paclitaxel as adjuvant therapy for women with 0-3 positive axillary lymph node breast cancer (3)
To determine the effect of long and short course CA and paclitaxel on the induction of menopause
for pre-menopausal patients. (4) To assess the discrepancy of myelosuppression among the
common MDR1 haplotypes in the CA treatment arm. (5) To assess the effect of MDR1 haplotypes
on DFS adjusted for treatment. (6) Exploratory analysis of the effect of CYP3A5, CYP2Cs and
CYP2B6 polymorphisms on DFS and toxicity.
Technical Approach: This is a randomized study and patients will be stratified according to
menopausal status (premenopausal vs postmenopausal) and estrogen receptor (ER)/progesterone
receptor (PR) status (ER and/or PR positive or unknown vs ER and PR negative). Patients are
randomized to 1 of 4 treatment arms. Arm I: Patients receive doxorubicin IV over 10-15 minutes
and cyclophosphamide IV on day 1. Treatment repeats every 21 days for 4 courses. Arm II:
Patients receive doxorubicin and cyclophosphamide as in arm I. Treatment repeats every 21 days
for 6 courses. Arm III: Patients receive paclitaxel IV over 1 hour once weekly for 12 weeks. Arm IV:
Patients receive paclitaxel as in arm III for 18 weeks. Treatment in all arms continues in the
absence of disease progression or unacceptable toxicity. Lumpectomy patients must then undergo
radiotherapy. Mastectomy patients undergo radiotherapy at the discretion of the treating
physician. Patients are followed every 6 months for 2 years and then annually for 15 years.
Progress: This protocol remains open to patient entry, with six patients enrolled. One patient is
currently receiving active treatment and the other five continued to be followed at MAMC during
FY06.
178
Detail Summary Sheet
Date: 30 Sep 06 Number: 202089 Status: Ongoing
Title: CTSU CALGB 49907, A Randomized Trial of Adjuvant Chemotherapy With Standard
Regimens, Cyclophosphamide, Methotrexate and Fluorouracil - (CMF) or Doxorubicin and
Cyclophosphamide - (AC), Versus Capecitabine in Women 65 Years and Older with Node
Positive or Node Negative Breast Cancer
Principal Investigator: LTC David E. McCune, MC
Department: Medicine/Hematology & Oncology Facility: MAMC
Associate Investigator(s): MAJ Angela G. Mysliwiec, MC; MAJ Jasmine T. Daniels, MC; LTC
Tommy A. Brown, MC
Start - Completion: Funding: Periodic Review:
12/5/2002 - Jul 2005 SWOG via Henry M. Jackson Foundation 5/22/2006
Study Objective: (1) To compare the effectiveness of standard chemotherapy (CMF or AC) with
single agent Capecitabine with respect to disease-free survival in women 65 years and older with
local and regional breast cancer. (2) To compare the effectiveness of standard chemotherapy
regimens with Capecitabine with respect to overall survival. (3) To determine the effects of each
treatment regimen on quality of life and physical function. (4) To assess the toxicity of each
treatment program. (5) To study the adherence to an oral chemotherapy regimen in older patients.
Technical Approach: This study compares the oral anti-cancer drug Capecitabine to standard
adjuvant therapy of Cyclophosphamide, Methotrexate and Fluorouracil, or Doxorubicin and
Cyclophosphamide in women who have complete breast cancer surgery and are over 65 years old.
The study will attempt to find a survival her forth difference in relapse rates or a quality of life.
Progress: This protocol is open to patient entry, with no patients enrolled.
179
Detail Summary Sheet
Date: 30 Sep 06 Number: 204124 Status: Completed
Title: CTSU CALGB 80303, A Randomized Phase III Trial of Gemcitabine plus Bevacizumab
(NSC #704865 IND #7921) Versus Gemcitabine plus Placebo in Patients With Advanced
Pancreatic Cancer
Principal Investigator: LTC David E. McCune, MC
Department: Medicine/Hematology & Oncology
Facility: MAMC
Associate Investigator(s): MAJ Jasmine T. Daniels, MC; MAJ Angela G. Mysliwiec, MC
Start - Completion: Funding:
1/25/2005 - Oct 2008 SWOG via Henry M. Jackson Foundation
Periodic Review:
8/19/2005
Study Objective: The primary objective is to determine if combination chemotherapy with
Gemcitabine and Bevacizumab achieves superior survival compared to Gemcitabine and Placebo in
patients with previously untreated advanced pancreatic cancer. Secondary objective is to compare
response rates, duration of response, progression free survival, and toxicity of these two regimens
in patients with advanced pancreatic cancer. Angiogenic biomarker studies are to measure
baseline levels of VEGF and correlate with treatment outcome, to measure baseline and on
treatment levels of additional growth factors that may be co- or counter-regulated with VEGF and
correlate with response to treatment, to measure baseline and treatment levels of coagulation and
endothelial cell activation markers and to generate protein expression profiles using a MALDI-
TOF based platform from serum samples. Pharmacogenomic predictors outcome is to assess any
differences in overall survival within the treatment arm (Gemcitabine+Bevacizumab), between the
two VEGF genotypic groups: Group I denoted by individuals with CT or TT genotypes and Group 2
consisting of individuals with CC genotypes., to conduct an exploratory analysis of gene-toxicity,
gene-response, and gene survival relationships. The clinical Economics of the study is to compare
the effects of Gemcitabine+Bevacizumab versus Gemcitabine+ Placebo on resource utilization,
cost, and utilities, and if applicable, to make estimates of marginal cost-utility.
Technical Approach: This study compares standard gemcitabine chemotherapy for advanced
pancreatic cancer to standard therapy plus Bevacizumab, a monoclonal antibody directed at
vascular endothelial growth factor. Eligible patients will be randomized to receive either
Gemcitabine plus Bevacizumab or Gemcitabine plus placebo. Each treatment group receives
therapy over a 28 day cycle. The study will compare response rates, toxicity and survival between
the two treatments in an attempt to establish a new standard of care.
Progress: The protocol was reported completed at MAMC in April 2006 when the study closed to
enrollment with one subject who enrolled during FY05, but died due to disease progression.
180
Detail Summary Sheet
Date: 30 Sep 06 Number: 202088 Status: Ongoing
Title: CTSU E1A00 A Randomized Phase III Trial of Thalidomide (NSC #66847) Plus
Dexamethasone versus Dexamethasone in Newly Diagnosed Multiple Myeloma
Principal Investigator: LTC David E. McCune, MC
Department: Medicine/Hematology & Oncology Facility: MAMC
Associate Investigator(s): MAJ Angela G. Mysliwiec, MC; MAJ Jasmine T. Daniels, MC; LTC
Tommy A. Brown, MC
Start - Completion: Funding: Periodic Review:
6/25/2002 - Jul 2005 SWOG via Henry M. Jackson Foundation 5/22/2006
Study Objective: 1) To evaluate the response rate and toxicity of thalidomide plus dexamthasone
and dexamethasone alone in patients with newly diagnosed myeloma. 2) To study the effect of
thalidomide on bone marrow microvessel density and angiogenesis grade and on the expression of
vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) in the
marrow.
Technical Approach: Compare a standard treatment for myeloma, dexamethasone to
dexamethasone plus thalidomide. The goal of the study is to see if there is any difference between
the two with respect to response rate, complications and quality of life or survival.
Progress: This protocol closed to patient entry in April 2003, with one patient enrolled who
continued to be followed at MAMC during FY06.
181
Detail Summary Sheet
Date: 30 Sep 06 Number: 204072 Status: Completed
Title: CTSU E3201 Intergroup Randomized Phase III Study of Postoperative Irinotecan, 5-
Fluorouracil and Leucovorin vs Oxaliplatin, 5-Fluorouracil and Leucovorin vs 5-Fluorouracil and
Leucovorin for Patients with Stage II or III Rectal Cancer Receiving Either Preoperative
Radiation and 5-Fluorouracil or Postoperative Radiation and 5-Fluorouracil
Principal Investigator: LTC David E. McCune, MC
Department: Medicine/Hematology & Oncology Facility: MAMC
Associate Investigator(s): MAJ Angela G. Mysliwiec, MC; LTC Tommy A. Brown, MC; MAJ
Jasmine T. Daniels, MC; LTC William B. Reece, MC; LTC John B. Halligan, MC
Start - Completion: Funding: Periodic Review:
8/2/2004 - May 2008 SWOG via Henry M. Jackson Foundation 4/25/2005
Study Objective: (1) To compare the overall survival of patients treated with Irinotecan, 5-FU
and Leucovorin versus those treated with Oxaliplatin, Leucovorin and 5-UF versus those treated
with Leucovorin and 5-FU for patients with Stage II and III rectal cancer. (2) To compare
sphincter preservation, tolerance of treatment and patterns of failure. (3) To prospectively assess
rectal function using the Patient Bowel Function/Uniscale questionnaire and the FACT Diarrhea
Subscale in patients treated with an adjuvant program of pelvic radiation therapy and
chemotherapy. (4) To correlate TS< DPD and TP expression (key targets for 5-FU); retention of
chromosome 18q alleles and MSI with TGF131RII mutation) (markers for 5-FU efficacy); and p53
gene mutation in tumor tissue specimens with treatment efficacy (5) To correlate tumor molecular
prognostic markers (chromosome 18q allelic loss and MSI) with survival. (6) To determine
physician preference in regard to the radiation-chemotherapy sequence in the Intergroup.
Technical Approach: The study compares standard adjuvant treatment for rectal cancer to two
different chemotherapy combinations to see if any regimen is superior for survival or toxicities. All
eligible patients with rectal cancer will be offered the study. Subjects will be offered one of three
chemotherapy combinations: (1) 5-FU + Leucovorin, (2) 5-FU + Leucovorin + Oxaliplatin, or (3) 5-
FU + Leucovorin + Irinotecan. Data will be collected on survival, toxicity, and relapse rates.
Toxicity will be assessed at each patient visit. Data will be analyzed centrally by CTSU.
Progress: ECOG announced permanent closure of this protocol effective 28 October 2005, no
patients enrolled at MAMC. This study has been redesigned and will soon open with a new study
number for new patient accrual.
182
Detail Summary Sheet
Date: 30 Sep 06 Number: 204043 Status: Ongoing
Title: CTSU IBCSG Trial 25-02, Tamoxifen and Exemestane Trial (TEXT), A Phase III Trial
Evaluating the Role of Exemestane Plus GnRH Analogue as Adjuvant Therapy for
Premenopausal Women with Endocrine Responsive Breast Cancer
Principal Investigator: LTC David E. McCune, MC
Department: Medicine/Hematology & Oncology Facility: MAMC
Associate Investigator(s): MAJ Jasmine T. Daniels, MC; MAJ Angela G. Mysliwiec, MC; LTC
Tommy A. Brown, MC; LTC Jane Shen-Gunther, MC
Start - Completion: Funding: Periodic Review:
5/12/2004 - Feb 2009 SWOG via Henry M. Jackson Foundation 1/24/2006
Study Objective: Evaluate the worth of ovarian function suppression (achieved by long-term use
of GnRH analogue) plus exemestane compared with Groh analogue plus Tamoxifen for
premenopausal women with steroid hormone receptor-positive early invasive breast cancer.
Technical Approach: This trial compares two different types of hormonal therapy for the
prevention of relapse after breast cancer surgery. Subjects may either receive no chemotherapy or
commence chemotherapy at the same time that GnRH analogue is initiated. Eligible subjects will
be randomized into one of two groups; surgery plus GnRH analogue and tamoxifen for 5 years or
surgery plus GnRH analogue plus exemestane for 5 years.
Progress: This protocol remains open to enrollment with one subject enrolled at MAMC, but had
to be transferred to Swedish Hospital and Medical Center, Seattle, WA.
183
Detail Summary Sheet
Date: 30 Sep 06 Number: 204035 Status: Ongoing
Title: CTSU NCIC CTG MA.27, A Randomized Phase III Trial of Exemestane Versus
Anastrozole in Postmenopausal Women With Receptor Positive Primary Breast Cancer
Principal Investigator: LTC David E. McCune, MC
Department: Medicine/Hematology & Oncology Facility: MAMC
Associate Investigator(s): MAJ Jasmine T. Daniels, MC; MAJ Angela G. Mysliwiec, MC; LTC
Tommy A. Brown, MC
Start - Completion: Funding: Periodic Review:
5/12/2004 - Jan 2010 SWOG via Henry M. Jackson Foundation 1/24/2006
Study Objective: Primary objective: Compare event free survival (EFS) between women treated
with exemestane or Anastrozole as adjuvant therapy. Secondary objectives: (1) To compare overall
survival(OS) of women treated with exemestane with that of those receiving Anastrozole as
adjuvant therapy, (2) To compare the time to distant recurrence for women treated with
exemestane with that for women receiving Anastrozole as adjuvant therapy, (3) To compare the
incidence of new primary contra lateral breast cancer in the different treatment groups, (4) To
compare the incidence of all clinical fractures and specifically hip and vertebral fractures in the
different treatment groups, and (5) To compare cardiovascular morbidity and morality (i.e.
significant coronary heart disease, which includes myocardial infarctions and angina requiring
percutaneous transluminal coronary angioplasty or coronary artery bypass graft, fatal and
nonfatal strokes and all vascular deaths) between exemestane and Anastrozole.
Note: Study objectives looking at the use of Celecoxib in this patient population were discontinued,
17 Dec. 04.
Technical Approach: This study compares two different aromatase inhibitors in an atempt to
establish standard of care for this type of breast cancer. Eligible subjects will be randomized to
receive either Exemestane or Anastrozole. reatment period will be 5 years except in cases of
unacceptable side effects or disease recurrence.
Note: The randomization in a double-blinded fashion to receive either Celecoxib or placebo was
discontinued Dec 04, due to increased frequency of fatal and non-fatal cardiovascular events
observed on the celecoxib arm of an NCI sponsored study of the prevention of colorectal polyps,
ntioned protocol has discontinued giving celecoxib/placebo to enrolled subjects, due to concerns
about the use of the Cox II inhibitor.
Progress: This protocol is closed to enrollment except for some sites that are performing specific
sub-studies. Ten patients enrolled at MAMC, and remain in treatment or follow-up during FY06.
184
Detail Summary Sheet
Date: 30 Sep 06 Number: 205071 Status: Terminated
Title: CTSU NSABP 80101 Phase III Intergroup Trial of Adjuvant Chemoradiation after
Resection of Gastric or Gastroesophageal Adenocarcinoma
Principal Investigator: LTC David E. McCune, MC
Department: Medicine/Hematology & Oncology Facility: MAMC
Associate Investigator(s): MAJ Angela G. Mysliwiec, MC; LTC William B. Reece, MC; LTC
John B. Halligan, MC; MAJ Jasmine T. Daniels, MC
Start - Completion: Funding: Periodic Review:
Never approved SWOG via Henry M. Jackson Foundation N/A
Study Objective: Primary objective: To determine whether overall survival is prolonged in
patients with resected gastric Adenocarcinoma who receive epirubicin, cisplatin, and infusional 5-
FU (ECF) before and after infusional 5-FU plus radiotherapy (RT) when compared to those treated
with bolus 5-FU and Leucovorin before and after infusional 5-FU plus RT. Secondary objectives.
(1) To determine disease-free survival and distant recurrence rates (2) To prospectively assess
whether expression of putative prognostic markers in the tumor correlate with overall survival (3)
To prospectively assess whether specific germ line polymorphisms related to chemotherapy
metabolism and resistance correlated with treatment-related toxicity and overall survival (4) To
prospectively assess whether serum levels of various growth factors correlated with overall
survival (5) To determine whether hospital procedure volume predicts recurrence-free and overall
survival
Technical Approach:
This is a randomized comparison of patients with completely resected gastric or gastroesophageal
cancer who receive ECF before and after infusional 5-FU plus RT versus patients who treated with
bolus 5-FU and Leucovorin before and after infusional 5-FU plus RT. The study will enroll 824
patients, male and female, age 18 and over, who have undergone complete resection of
adenocarcinoma of the stomach or gastroesophageal junction. Up to 10 patients will participate at
MAMC. Patients will be assessed at screening with history and physical exam, height, weight,
vitals, laboratory tests including hematology, chemistry and liver functions, CT of the abdomen
and pelvis, and chest x-ray if indicated. Women of child-bearing potential will have a serum
pregnancy test. A laboratory sample (4.5 ml of blood) will also be drawn for patients participating
in the 60201 sub-study.
For patients enrolled in Arm A (5-FU, Leucovorin) all laboratory tests will be performed
weekly for each cycle of 5-FU and Leucovorin (cycles 1, 3 and 4) and weekly during RT (cycle 2).
For patients enrolled in Arm B (EPC, 5-FU) all laboratory tests will be performed weekly during
radiation therapy and weekly during chemotherapy cycles. Patients will also be followed during
treatment with physical exam at the beginning of each cycle, including vital signs, weight, and
toxicity assessment. After treatment is completed, physical exam including vital signs, weight and
laboratory tests will be repeated every 3 months for 2 years, every 4 months for 2 years, then
yearly for 3 years (7 years total). Disease progression will be assessed by chest x-ray as indicated,
at week 30 then yearly for 5 years, and at time of initial tumor progression.
Patients will be provided with nutritional counseling, and monitored for weight loss
throughout the treatment portion of the study. Weight loss of > 5% of pretreatment weight will
trigger mandatory intervention such as oral supplements, nasal-intestinal feeding tubes,
jejunostomy and intravenous alimentation depending on the needs of the patient.
Progress: This protocol received initial IRB approval, 26 Apr 05, but was administratively
terminated by the IRB prior to final approval in October 2005, for failure to comply with IRB
stipulations.
185
Detail Summary Sheet
Date: 30 Sep 06 Number: 202043
Status: Ongoing
Title: CTSU RTOG 98-04: Phase III Trial of Observation +/- Tamoxifen vs.
Good Risk Duct Carcinoma In-Situ (DCIS) of the Female Breast
RT +/- Tamoxifen for
Principal Investigator: LTC David E. McCune, MC
Department: Medicine/Hematology & Oncology
Facility: MAMC
Associate Investigator(s): MAJ Angela G. Mysliwiec, MC; MAJ Jasmine T. Daniels, MC; LTC
Tommy A. Brown, MC
Start - Completion: Funding:
2/26/2002 - Feb 2005 SWOG via Henry M. Jackson Foundation
Periodic Review:
1/24/2006
Study Objective: (1) Comparing whole breast radiation +/- Tamoxifen compared to wide excision
to negative margins alone +/- Tamoxifen, in decreasing or delaying the appearance of local failure,
both invasive and in situ, and preventing need for mastectomy, (2) assess distant disease free
survival patients in either arm who fail with progression can be successfully salvaged with further
definitive local therapy and adjuvant systemic therapy, (3) setting up a working pathology
classification system for DECIS, (4) establishing an epidemiological questionnaire registry for
companion studies of biomarkers, and (5) establish tissue bank of patients who progress to local
failure in study breast.
Technical Approach: To compare the efficacy of Tamoxifen with or without whole breast
radiation, in decreasing or delaying the appearance of local failure, both invasive and in- situ, and
preventing the need for mastectomy in women with ductal carcinoma in-situ (DCIS) of the breast.
Progress: This protocol remains open to patient entry, with no patients enrolled.
186
Detail Summary Sheet
Date: 30 Sep 06 Number: 206112 Status: Ongoing
Title: CTSU/GOG 0218 A Phase III Trial of Carboplatin and Paclitaxel Plus Placebo Versus
Carboplatin and Paclitaxel Plus Concurrent Bevacizumab (NSC #704865, IND #7921) Followed
By Placebo, Versus Carboplatin and Paclitaxel Plus Concurrent and Extended Bevacizumab, In
Women With Newly Diagnosed, Previously Untreated, Suboptimal Advanced Stage Epithelial
Ovarian and Primary Peritoneal Cancer
Principal Investigator: LTC David E. McCune, MC
Department: Medicine/Hematology & Oncology Facility: MAMC
Associate Investigator(s): MAJ Jasmine T. Daniels, MC; MAJ Angela G. Mysliwiec, MC; LTC
Louis A. Dainty, MC
Start - Completion: Funding: Periodic Review:
11/2/2006 - Sep 2011 SWOG via Henry M. Jackson Foundation N/A
Study Objective: Primary objectives: Determine if the addition of 5 concurrent cycles of
Bevacizumab to 6 cycles of standard treatment (carboplatin and paclitaxel) [Arm II] reduces the
death rate when compared to 6 cycles of standard treatment alone [Arm I] in women with newly
diagnosed suboptimal advanced epithelial ovarian and peritoneal primary cancer; determine if the
addition of 5 concurrent cycles plus extended Bevacizumab for 15 months total treatment time to 6
cycles of standard therapy (carboplatin and paclitaxel) [Arm III] reduces the death rate when
compared to 6 cycles of standard therapy [Arm I] in this subset of patients.
Secondary objectives: Determine, in the event that both Arm II and Arm III regimens are superior
to the Arm I regimen with respect to overall survival, whether the Arm III regimen reduces the
death rate when compared to the Arm II regimen; determine whether the Arm II or Arm III
regimen increases the duration of progression-free survival when compared with the Arm I
regimen; compare each of the experimental regimens to the Arm I regimen with respect to the
incidence of severe side effects or serious adverse events; determine the impact on quality of life
following treatment with the above regimens; assess the relationship between angiogenic markers
and clinical outcome (tumor response, progression-free survival, overall survival) in each of the
Arms; assess the predictive value of a set of genes whose expression correlates with survival in
these patients.
Technical Approach: This is a Phase III study of standard chemotherapy (carboplatin plus
paclitaxel) versus standard plus concurrent bevacizumab versus standard plus extended
bevacizumab in women with first line, advanced stage epithelial ovarian and primary peritoneal
cancer. Patients with a histological diagnosis of FIGO Stage III or IV epithelial or peritoneal
primary cancer, with suboptimal residual disease following initial surgery will be screened for
enrollment. Patients who qualify will be enrolled and randomized in a 1:1:1 ratio to Arm I, II or
III. Randomization will be stratified by stage of disease (Stages III versus IV) and by performance
status (0 versus 1 or 2). All patients will receive standard chemotherapy, paclitaxel 175 mg/m2 IV
over 3 hours followed by carboplatin AUC 6 IV over 30 minutes on Day 1 of a 21 day cycle, over 6
cycles. Dose adjustments will be made per protocol for changes in creatinine clearance and for
toxicities. Patients in Arm I will also receive placebo on Dayl of Cycle 2 through 6, the placebo
every 21 days for an additional 15 months. Patients on Arm II will receive bevacizumab on Day 1
of Cycle 2 through 6, and placebo every 21 days for an additional 15 months. Patients on Arm III
will receive bevacizumab on Day 1 of Cycle 2 through 6, and bevacizumab every 21 days for an
additional 15 months. Bevacizumab will be given, 15 mg/mg, IV, per package insert. During initial
chemotherapy, patients will be assessed at the start of each cycle by physical exam, laboratory
tests including CBC, chemistry, LFTs, and CA-125. Patients on anticoagulant therapy will have a
repeat PT, PTT and INR prior to each cycle. Blood pressure will be monitored at least weekly
187
during the first cycle, then prior to each cycle afterwards. Radiographic measurements will be
repeated prior to every other cycle. During bevacizumab/placebo treatment these same
assessments will be done every other cycle. Post treatment, patients will be followed every 3
months for 2 years, every 6 months for three years, then annually.
Progress: This greater than minimal risk protocol received initial approval with stipulations
during the convened IRB meeting on 25 July 2006. CIRO approval was obtained 2 November 2006.
188
Detail Summary Sheet
Date: 30 Sep 06 Number: 206054 Status: Ongoing
Title: NSABP B-38 A Phase III Adjuvant Trial Comparing Three Chemotherapy Regimens in
Women with Node-Positive Breast Cancer: Docetaxel/Doxorubicin/Cyclophosphamide (TAC);
Dose-Dense (DD) Doxorubicin/Cyclophosphamide Followed by DD Paclitaxel (DD AC-P); DD
Doxorubicin/Cyclophosphamide Followed by DD Paclitaxel Plus Gemcitabine (DD AC-PG)
Principal Investigator: LTC David E. McCune, MC
Department: Medicine/Hematology & Oncology Facility: MAMC
Associate Investigator(s): MAJ Jasmine T. Daniels, MC; MAJ Angela G. Mysliwiec, MC
Start - Completion: Funding: Periodic Review:
4/12/2006 - Feb 2011 CTSU N/A
Study Objective: The primary aims of this study are to determine whether the DD AC/PG
regimen is superior to the TAC regimen as well as to the DD AC/P regimen in improving disease-
free survival and to compare the relative disease-free survival of TAC and DD AC/P. Secondary
aims are to determine whether DD AC/PG is superior to TAC as well as to DD AC/P in improving
overall survival, recurrence-free interval, and distant recurrence-free interval; to compare overall
survival, recurrence-free interval, and distant recurrence-free interval of the TAC and DD AC/P
regimens, and to compare the relative toxicities of the three regimens.
Technical Approach: This Phase III adjuvant therapy trial for women with node-positive breast
cancer will compare three regimens of chemotherapy: (1) TAC: docetaxel, doxorubicin, and
cyclophosphamide every 3 weeks for 6 cycles, (2) DD AC/P: doxorubicin/cyclophosphamide every 2
weeks for 4 cycles followed by paclitaxel every 2 weeks for 4 cycles (3) DD AC/PG:
doxorubicin/cyclophosphamide every 2 weeks for 4 cycles followed by paclitaxel plus gemcitabine
every 2 weeks for 4 cycles. Women with operable, invasive carcinoma of the breast with
histologically positive axillary nodes will be enrolled and stratified by number of positive nodes,
hormone receptor status, and type of surgery and planned radiotherapy. Following stratification,
patients will be randomized to one of the three chemotherapy regimens. Women with ER positive
and/or PgR-positive tumors should receive hormonal therapy for a minimum of 5 years following
completion of chemotherapy. All women who have had a lumpectomy will have radiation therapy.
Chest wall and regional nodal irradiation will be prospectively determined at the discretion of the
investigator and will be used as a stratification factor. For patients who agree to specimen
banking, index tumor blocks as well as tumor blocks collected after diagnosis of contralateral
breast cancer will be submitted. Serum will be collected at baseline, at the time of first
locoregional or distant recurrence, and when a contralateral breast cancer develops prior to
locoregional or distant recurrence. If the first recurrence is an ipsilateral breast tumor recurrence,
a serum sample will also be collected at the time of the first subsequent regional or distant
recurrence. The study will enroll 4800 patients over a period of approximately 4 years. It is
anticipated that the definitive analysis will be carried out approximately 7 years after study
initiation.
Progress: This protocol remains open to patient entry, with one patient enrolled during FY06.
Multiple external adverse events have been reported.
189
Detail Summary Sheet
Date: 30 Sep 06 Number: 206073
Status: Ongoing
Title: Phase 1/2 study of ZK-Epothilone (ZK-Epo; ZK 219477) in combination with carboplatin in
patients with platinum-sensitive, recurrent ovarian cancer
Principal Investigator: LTC David E. McCune, MC
Department: Medicine/Hematology & Oncology
Facility: MAMC
Associate Investigator(s): MAJ Jasmine T. Daniels, MC; MAJ Angela G. Mysliwiec, MC
Start - Completion: Funding:
7/11/2006 - May 2010 Berlex Laboratories via Henry M. Jackson
Foundation
Periodic Review:
N/A
Study Objective: Primary objective: to establish a dose of ZK-Epo to be used in combination with
carboplatin in the subsequent Part 2 of the study. Secondary objective: to investigate the
pharmacokinetics of ZK-Epo and carboplatin when given as a combination. Part 2: Primary
objective: to investigate the efficacy of ZK-Epo in combination with carboplatin in patients with
platinum-sensitive, recurrent ovarian cancer in progression following a first regimen of
chemotherapy. Secondary objective: to investigate the safety and tolerability of ZK-Epo in
combination with carboplatin in this patient population.
Technical Approach: This is a Phase I / II, open label study of ZK-Epothilone (ZK 219477) in
combination with carboplatin in patients with platinum sensitive, recurrent ovarian cancer.
Patients will be eligible who have progressed after having had one prior chemotherapy regimen
including a platinum compound, and who have had a response lasting between 6 and 24 months.
Phase I of the study will enroll up to 18 patients in cohorts of 6. Patients will initially be treated at
12 mg/m2. Depending on the observed Dose Limiting Toxicities (DLT) the dose will either be
decreased to 9 mg/m2 or increased to 15 mg/m2. Patients who develop a DLT will be withdrawn
from the study. Patients in Phase I will be required to participate in a pharmacokinetic study to
examine the metabolism of ZK-Epo in combination with carboplatin. Patients may also participate
in an optional pharmacogenetic substudy. Patients who participate in Part I who appears to
benefit from treatment can continue to receive additional cycles of ZK-Epo at the dose level at
which they started treatment. Phase II of the study will use the treatment dose determined in
Phase I. Up to 30 patients will be enrolled, for a total of 32 evaluable patients. Patients in both
phases will be scheduled to receive 2 to 6 cycles of treatment. ZK-Epo will be given per dose
escalation, as a 3-hour IV infusion, on Day 1 of a 21 day cycle. Carboplatin will be given at an AUC
of 5, as a 30 minute infusion, after ZK-Epo. Patients will sign an approved consent form prior to
any study-related procedures. Initial evaluation will include physical exam and history, review in
inclusion criteria, disease assessment by CT, MRI or CA-125 level, EKG, and laboratory tests
including CBC, chemistry and LFT's. PE and labs will be repeated for each cycles, disease
assessment will be repeated every other cycle. Patients will continue treatment until they have
received 6 cycles, progress, or are unable to tolerate treatment. After treatment patients will be
followed until disease progression. Pharmacokinetic studies will be done for all patients on Phase
I, and is option for patients on Phase II. This will consist of thirteen 2.7ml samples drawn within
the first 12 hours, and one sample on days 2, 3, 4, 5, 8 and 15. PK samples will only be drawn for
the first two cycles of a patient's treatment. Additional pharmacogenetic studies are optional for
all patients, and consist of a single blood sample drawn prior to initiation of therapy.
Progress: This protocol is open to patient entry, but patient enrollment has not been initiated
pending the outcome of discussions with the study sponsor concerning the cost language in the
MAMC informed consent document.
190
Detail Summary Sheet
Date: 30 Sep 06 Number: 204008
Status: Ongoing
Title: Phase II Trial of ONTAK® in Refractory or Relapsed Advanced Non-small Cell Lung
Cancer (NSCLC)
Principal Investigator: LTC David E. McCune, MC
Department: Medicine/Hematology & Oncology
Facility: MAMC
Associate Investigator(s): MAJ Angela G. Mysliwiec, MC; MAJ Jasmine T. Daniels, MC
Start - Completion: Funding:
1/8/2004 - Nov 2005 Ligand Pharmaceuticals, Inc. via Henry M.
Jackson Foundation
Periodic Review:
10/19/2006
Study Objective: (1) To evaluate the safety of ONTAK® (denileukin diftitox, DAB389IL-2) in
patients with NSCLC, (2) To evaluate the efficacy of ONTAK® in patients with NSCLC. (3) To
evaluate the value of soluble Interleuikin-2 receptors (IL2R) in predicting tumor response (or
reaction) to ONTAK®. (4) To evaluate the correlation between tumor IL2R status and disease
response to treatment.
Technical Approach: This is a Phase II multicenter non-randomized open label clinical trial. Up
to 50 subjects will be enrolled in the overall study with a goal of having 42 evaluable subjects. At
MAMC, 2-4 subjects may be enrolled from subjects receiving treatment for lung cancer in the
Hematology and Oncology Clinic. Treatment will consist of IV administration of ONTAK® daily for
5 days every 3 weeks. Safety assessments will include laboratory hematology and blood chemistry
tests, physical exam and vital signs, and ECOG status and toxicity assessments.
During the first cycle of treatment, toxicities will be evaluated weekly using the NCI Common
Toxicity Criteria, then each cycle afterwards. Serious Adverse Events will be reported to the IRB,
FDA, and to the study drug manufacturer. Tumor response will be assessed by physical exam, CT
scan, and other appropriate imaging studies performed every 2 cycles and evaluated using the
RECIST criteria. Subjects with tumor response or stable disease will receive up to 6 cycles of study
treatment. Subjects with progressive disease or unacceptable toxicity will be removed from the
study. Interim evaluation is planned after the first 14 evaluable subjects. If no subjects experience
an objective response or stable disease, then the study will be terminated. Soluble IL2 receptor
(IL2R) levels in serum will be measured to study the value in predicting tumor reaction or
response to the treatment, and evaluation of tumor IL2R status and CD 25 staining will be
performed by the central study site laboratory. Primary efficacy endpoints are the response rate,
overall survival, and time to disease progression. Primary safety endpoints are the number of
cycles of therapy administered and the type and grade of toxicities. Secondary endpoints will be
the level of soluble IL-2 receptor in serum and receptor expression in the tumor tissue (positive or
negative).
Progress: This protocol closed to enrollment with two subjects enrolled. One subject is deceased
and the other subject continued to be followed during FY06.
191
Detail Summary Sheet
Date: 30 Sep 06 Number: 206084 Status: Ongoing
Title: Pilot Study to Evaluate the Safety and Efficacy of PROCRIT (Epoetin alfa) 80,000 Units
Once Every Four Weeks (Q4W) vs. 40,000 Units Once Every Two Weeks (Q2W) in Cancer
Patients with Non-Chemotherapy Anemia
Principal Investigator: LTC David E. McCune, MC
Department: Medicine/Hematology & Oncology
Facility: MAMC
Associate Investigator(s): MAJ Jasmine T. Daniels, MC; MAJ Angela G. Mysliwiec, MC
Start - Completion: Funding:
7/12/2006 - Dec 2009 Henry M. Jackson via Henry M. Jackson
Foundation
Periodic Review:
N/A
Study Objective: Objectives: To investigate the safety and efficacy of PROCRIT 80,000 units (U)
once every 4 weeks and 40,000U once every 2 weeks subcutaneously in anemic subjects with
cancer not receiving chemotherapy or radiation therapy and to assess the effects of the dosing
regimens on time-to- hematopoietic-response, and transfusion requirements.
Technical Approach: This is a prospective, randomized, open-label, multi-center pilot study to
evaluate the safety and efficacy of PROCRIT (Epoetin alfa) 80,000 Units once every four weeks
versus 40,000 Units (U) once every two weeks in cancer patients with non-chemotherapy anemia.
A total of 100 subjects will be enrolled and up to 10 at MAMC. Patients with confirmed non-
myeloid malignancy, who are anemic, and not receiving chemotherapy or radiation will be
randomized in to one of two treatment groups receiving Procrit. Safety data that will be obtained
during the study includes height, weight, blood tests, blood pressure and incidence and severity of
adverse events. Patients will be randomized to one of two treatments groups receiving PROCRIT
subcutaneously. The starting dose will be either 80,000 U every 4 weeks with a maximum
treatment period of 13 weeks or 40,000 U every 2 weeks with a maximum period of 15 weeks. A
follow-up visit will occur for both treatment groups on weeks 17. Hemoglobin levels will be
obtained every week to monitor hemoglobin rate of rise for safety. The target hemoglobin is 10 to
12 g/dL. Patient will be screened for study eligibility at the screening visit occurring up to 14 days
prior to treatment with study drug unless otherwise specified. They will be followed up to week 17.
An interim analysis will be performed when the first 40 enrolled subjects have completed or
withdrew from the study. The primary efficacy end point will be hematopoietic response, defined
as < 1 g/dL rise in hemoglobin.
Progress: This protocol remains open to patient entry, with no patients enrolled.
192
Detail Summary Sheet
Date: 30 Sep 06 Number: 204080
Status: Ongoing
Title: Protocol U2963n: The National Lymphocare Study: An Observational Study of Treatment,
Outcomes, and Prognosis in Patients With Follicular Non-Hodgkin's Lymphoma
Principal Investigator: LTC David E. McCune, MC
Department: Medicine/Hematology & Oncology
Facility: MAMC
Associate Investigator(s): MAJ Angela G. Mysliwiec, MC; MAJ Jasmine T. Daniels, MC
Start - Completion: Funding:
8/16/2004 - Aug 2014 Genentech via Henry M. Jackson Foundation
Periodic Review:
5/22/2006
Study Objective: The objective of this study is to delineate differences in treatment outcome for
patients with follicular non-Hodgkin's lymphoma (NHL) by comparing the outcomes and safety of
common front-line and subsequent therapeutic strategies. The planned comparisons address
clinical questions including the role of watchful waiting, use of anthracyclines in front-line
therapy, and role of maintenance therapy, and treatment sequencing. Reported outcomes for a
given treatment strategy will include a description of these outcomes based on Follicular
Lymphoma International Prognostic Index (FLIPI) score risk stratification at the time of diagnosis
and subsequent treatment initiation.
Technical Approach: This is a prospective, observational, longitudinal, multicenter study of
patients with newly diagnosed follicular Non-Hodgkin's Lymphoma (NHL). 12-18 patients may be
enrolled at MAMC, and approximately 5000 patients in the United States. A database will be
created containing patient and tumor characteristics and treatment and outcome information. All
patients at participating sites diagnosed with follicular NHL within 6 months prior to enrollment
will be eligible, regardless of specific treatments received (including investigational products) and
including patients followed using a watch-and-wait approach. Patients will receive treatment and
evaluations for NHL according to the treating physician's standard of care and clinical practice. No
study- specific visits, interventions or patient evaluations will be conducted. Patient data will be
collected from medical records and reported by means of a Web-based Electronic Data Collection
System (EDC). All treatments patients receive for NHL will be recorded and treatment outcomes
will be collected quarterly. Enrolled patients will be followed for up to 10 years or until death,
withdrawal of consent, loss to follow up, or study termination. Study feasibility reviews will be
conducted at 2, 5, 7, and 10 years. Outcome measures include: time from initial diagnosis to initial
therapy; time from initial therapy to subsequent therapy, response to treatment (initial and
subsequent) as assessed by the treating physician; time to disease progression; survival time;
lymphoma treatment-related toxicity as measured by death, early treatment discontinuation, and
hospitalization; and FLIPI score. This is an observational cohort study and is not designed to
evaluate a predefined hypothesis. However, effectiveness and safety outcomes will be analyzed,
confidence intervals for differences will be reported, and standard statistical tests will be
performed, with the first evaluation taking place after approximately 500 patients have been
enrolled for at least 6 months.
Progress: This protocol remains open to enrollment with four subjects consented. One subject has
died and three continued to be followed at MAMC during FY06.
193
Detail Summary Sheet
Date: 30 Sep 06 Number: 202107 Status: Completed
Title: Randomized Study of Docetaxel Versus Docetaxel Plus GenasenseTM (G3139; Bcl-2
Antisense Oligonucleotide) in Patients with Previously Treated Non-Small Cell Lung Cancer,
No. N304
Principal Investigator: LTC David E. McCune, MC
Department: Medicine/Hematology & Oncology
Facility: MAMC
Associate Investigator(s): MAJ Angela G. Mysliwiec, MC; MAJ Jasmine T. Daniels, MC
Start - Completion: Funding:
9/30/2002 - Sep 2004 Genta Inc via Henry M. Jackson Foundation
Periodic Review:
8/29/2006
Study Objective: (1) To compare the survival of subjects with advanced non-small cell lung
cancer treated with docetaxel alone versus docetaxel combined with Genasense (Bcl-2 antisense
oligonucleotide). (2) To compare response, time to progression, tumor-related symptoms, and safety
in the two treatment groups.
Technical Approach: In this advanced non-small cell lung cancer study antisense treatment will
be given with Taxotere (docetaxel) and tumor response and safety will be compared to therapy
with Taxotere alone. This study is a randomized, multicenter, open label, Phase III design clinical
trial. This Phase III study will include a minimum of 280 patients randomized in a 1:1 ratio to
Docetaxel or Docetaxel + Genasense. Approximately 35 centers will participate. Study endpoints
include the primary efficacy variable of survival and secondary efficacy variables of response rate,
proportion of patents surviving at 6 and 12 months, duration of response, time to disease
progression and other measures of clinical benefit such as change in performance status. All
patients in the study will be prospectively stratified by response to prior chemotherapy regimen,
ECOG performance status and prior paclitaxel treatment.
Progress: This protocol closed to enrollment in July 2004, when accrual goals were met. Three
subjects enrolled at MAMC; all were reported deceased by July 2005, due to disease progression. A
site close out visit was reported in September 2006.
194
Detail Summary Sheet
Date: 30 Sep 06 Number: 206055
Status: Ongoing
Title: SWOG S0424: Molecular Epidemiology Case-Series Study of Non-Small Cell Lung Cancer
in Smoking and Non-Smoking Women and Men
Principal Investigator: LTC David E. McCune, MC
Department: Medicine/Hematology & Oncology
Facility: MAMC
Associate Investigator(s): MAJ Jasmine T. Daniels, MC; MAJ Angela G. Mysliwiec, MC
Start - Completion: Funding:
8/3/2006 - Feb 2011 SWOG via Henry M. Jackson Foundation
Periodic Review:
N/A
Study Objective: To assess lung tissue from cancer patients for specific tobacco smoke
carcinogens, alterations in specific genes, and to determine whether these factors differ by gender
and smoking status, adjusting for potential exposures and influential factors including family
smoking status, medication use, hormonal and reproductive factors. To measure levels of (PAH)-
DNA adducts in tissues and see if levels are higher in females than males for the same level of
smoking.
Technical Approach: Eligible patients would be asked to complete a questionnaire about
smoking, reproductive history, occupational exposures and other factors. Samples of cancer tissue
obtained at the time of biopsy or operation would be sent to a special laboratory to study genetic
changes that may explain why women are more susceptible to tobacco smoke chemicals. A blood
specimen would be sent to a special laboratory for scientific testing to help learn more about the
causes of lung cancer and who is at risk to identify who would benefit from intensive screening and
possible interventions. The results of the testing will not be released to the patient or study
physician.
Progress: This protocol is open to patient entry, with no patients enrolled during FY06.
195
Detail Summary Sheet
Date: 30 Sep 06 Number: 206013
Status: Ongoing
Title: SWOG S0435 A Phase II Trial of BAY 43-9006 (SNC-724772) in Patients with Platinum-
Treated Extensive Stage Small Cell Lung Cancer
Principal Investigator: LTC David E. McCune, MC
Department: Medicine/Hematology & Oncology
Facility: MAMC
Associate Investigator(s): MAJ Jasmine T. Daniels, MC; MAJ Angela G. Mysliwiec, MC
Start - Completion: Funding:
1/18/2006 - Nov 2010 SWOG via Henry M. Jackson Foundation
Periodic Review:
11/21/2006
Study Objective: Primary endpoints: to evaluate the efficacy of BAY 43-9006 in previously-
treated, platinum-sensitive and platinum-refractory patients with measurable disease and
extensive stage small cell lung cancer (E-SCLC) in terms of response rate (confirmed and
unconfirmed, complete and partial). Secondary endpoints: to assess the qualitative and
quantitative toxicities of BAY 43-9006 in this patient population. To assess overall survival in this
group of patients treated with BAY 43-9006. To collect specimens via the Lung Cancer Specimen
Repository Protocol (S9925) in order to perform exploratory analyses of the relationship between
selected markers and patient outcomes.
Technical Approach: This is a Phase II, multi-center trial of BAY 43-9006 in patients with
platinum-treated extensive stage small cell lung cancer. BAY-43-9006, or Sorafenib, is a compound
that inhibits multiple tyrosine kinase pathways involved in tumor progression. Patients will be
enrolled who have had prior treatment with platinum based therapy. Accrual will proceed
separately in two strata based on whether patients are platinum sensitive or resistant. Patients
will undergo screening, with medical history and physical, head and chest CT scans, bone scan if
indicated, and blood tests for chemistry and CBC. Patients will also be offered participation in
S9925, a companion study for specimen submission. Eligible patients will be treated with an oral
dose of BAY 43-9006, 400mg twice a day in a 4 week cycle until disease progression. Ongoing
assessments will include weekly toxicity assessment, CBC every other week, and physical exam
chemistry every 4 weeks. Disease assessment will include scans every 8 weeks during treatment,
and every 3 months after treatment for up to 2 years after enrollment, or until death. Enrollment
will continue until 20 each of platinum sensitive and platinum resistant patients have been
enrolled, after which an additional 20 patients will be enrolled to each group if there has been at
least one response to treatment.
Progress: This protocol remains open to patient entry to the platinum refractory arm of the study.
One patient enrolled during FY06, but died of progressive disease after declining further
treatment due to serious adverse events of gait instability, slurred speech and confusion.
196
Detail Summary Sheet
Date: 30 Sep 06 Number: 205036 Status: Ongoing
Title: CTSU NSABP C-08, A Phase III Clinical Trial Comparing Infusional 5-Fluorouracil (5-
FU), Leucovorin, And Oxaliplatin (mFOLFOX6) Every Two Weeks With Bevacizumab To The
Same Regimen Without Bevacizumab For The Treatment Of Patients With Resected Stages II
And III Carcinoma of the Colon
Principal Investigator: MAJ Angela G. Mysliwiec, MC
Department: Medicine/Hematology & Oncology Facility: MAMC
Associate Investigator(s): LTC David E. McCune, MC; MAJ Jasmine T. Daniels, MC
Start - Completion: Funding: Periodic Review:
5/3/2005 - Mar 2009 SWOG via Henry M. Jackson Foundation 1/24/2006
Study Objective: Primary Objective is to compare the relative efficacy of mFOLFOX6 +
bevacizumab with that of mFOLFOX6 alone in prolonging disease-free survival (DFS). Secondary
Objective is to compare the relative efficacy of mFOLFOX6 + bevacizumab with that of
mFOLFOX6 alone in prolonging survival (S).
Technical Approach: Eligible subjects will be randomized into one of the two study groups.
Patients in Group 1 will receive the drugs 5-FU, Leucovorin, and Oxaliplatin, repeated every 14
days (one cycle) for a total of 12 cycles of chemotherapy. Patients in Group 2 will receive 5-FU,
Leucovorin, and Oxaliplatin, repeated every 14 days (one cycle) for a total of 12 cycles of
chemotherapy and also receive bevacizumab on day 1 of each cycle before receiving the
chemotherapy. After chemotherapy is done, subjects will continue to receive bevacizumab once
every 2 weeks for another 6 months. Subjects will continue to be followed for the first 5 years with
physical exams, urine and blood tests, and an enema with x-ray or endoscopic exam. National
accrual is expected to be 2632 patients over 4 years. Investigators estimate approximately 4
patients per year for a total of 16 patients enrolled at MAMC.
Progress: This study closed to enrollment 6 October 2006 after NSABP enrollment goals were
met. Four patients enrolled at MAMC and remained in treatment or follow-up during FY06.
197
Detail Summary Sheet
Date: 30 Sep 06 Number: 206025 Status: Terminated
Title: RegistHER: An Observational Cohort Study of Patients with HER2-Positive Metastatic
Breast Cancer
Principal Investigator: MAJ Angela G. Mysliwiec, MC
Department: Medicine/Hematology & Oncology Facility: MAMC
Associate Investigator(s): MAJ Jasmine T. Daniels, MC; LTC David E. McCune, MC
Start - Completion: Funding: Periodic Review:
12/14/2005 - Jan 2011 DCI N/A
Study Objective: Objectives are to describe the time to treatment failure, time to disease
progression, overall survival, incidence of clinically significant cardiac-related adverse events in a
cohort of patients with HER2-positive metastatic breast cancer and to describe and compare the
outcomes associated with common therapies.
Technical Approach: This is a prospective observational cohort study designed to describe the
effectiveness and safety (treatment outcomes and clinically significant cardiac adverse events) in
patients with HER2-positive metastatic breast cancer. Enrolled patients will receive treatment
and evaluations for HER2-positive metastatic breast cancer as determined by their treating
physicians according to the standard of care and clinical judgement. The study will enroll > 1000
patients over approximately 2-3 years. Patients will be followed from enrollment until death,
withdrawal of consent, or loss to follow-up.
Progress: This protocol was terminated 2 March 2006, due to failed contract negotiations with the
study sponsor. The study was never initiated at MAMC.
198
Detail Summary Sheet
Date: 30 Sep 06 Number: 204082 Status: Ongoing
Title: Evaluating Cognitive Function in Women Receiving Chemotherapy for Newly Diagnosed
Breast Cancer
Principal Investigator: Margaret J. Ramsdell, RN, BSN, OCN
Department: Medicine/Hematology & Oncology Facility: MAMC
Associate Investigator(s): Donna L. Berry, Ph.D., RN
Start - Completion: Funding: Periodic Review:
5/25/2004 - Oct 2004 DCI 5/22/2006
Study Objective: To evaluate cognitive function in women newly diagnosed with breast cancer,
receiving chemotherapy and the effect of cognitive function on the individual's quality of life. This
study will examine both the relationship between cognitive function scores and patient's self-
reported cognitive problems and the meaning of the measures for women receiving chemotherapy
for breast cancer. Specifically: (1) to describe function scores of the EORTC QLQ C-30 cognitive
subscale and the High Sensitivity Cognitive Screen (HSCS) in women with breast cancer at
baseline and mid point in chemotherapy treatment for breast cancer, and (2) to evaluate the
process and meaning of answers on the HSCS and the cognitive subscale questions of the EORTC
QLQ C-30 questionnaire.
Technical Approach: This study will utilize a longitudinal, pre-post test design to evaluate
women newly diagnosed with breast cancer who will be receiving doxorubicin and
cyclophosphamide. Women ages 25-70, newly diagnosed with breast cancer will be asked to
participate in this study. Subjects interested will fill out a 3x5 card with name and phone number
and will be contacted by the PI. After signing consent and answering questions, patients will fill
out the EORTC QLQ C-30 questionnaire. Upon completion of the EORTC QLQ C-30 a cognitive
interview of those questions will be conducted to find out how the subjects felt about reading and
answering the questions, what those quesitons mean to them and how their cognitive function
currently is affecting their quality of life. The HSCCS, a sensitive tool for detecting subtle
cognitive impairment, will be administered at the completion of the cognitive interview.
Descriptive statistics will be used to summerize the demographic characteristics of the EORTC
QLQ C-30 cognitive scale scores and the cognitive domain scores on the HSCS of the subjects of
two time points per chemotherapy and at mid point during chemotherapy. The Mann- Whitney test
will be used to compare cognitive scale scores on the EORTC QLQ C-30 and cognitive domain
scores on the HSCS in subjects at the same time point. The results at both time points will be
graded and examined for changes in scores on the HSCS as well as changes in the five item
subscale of the EORTC QLQ C-30 .
Progress: This protocol closed to enrollment in May 2006, with 6 subjects enrolled. Data collection
is complete and the study remains ongoing to complete data analysis and the final manuscript.
199
Detail Summary Sheets
Internal Medicine Service, Department of
Medicine
200
Detail Summary Sheet
Date: 30 Sep 06 Number: 205046
Status: Ongoing
Title: The Effect of Blood Transfusion on Serum Ferritin and Iron
Principal Investigator: CPT Corinna Avalos, MC
Department: Medicine/Internal Medicine
Facility: MAMC
Associate Investigator(s): CPT Ashley A. Feaver, MC; LTC Rajat Bannerji, MC; CPT Daniel
G. Cuadrado, MC; COL Ronald H. Cooper, MC; CPT Patrick M. McNutt, MS
Start - Completion: Funding:
5/26/2005 - Mar 2006 DCI
Periodic Review:
1/24/2006
Study Objective: To study the effect of packed red blood cell transfusion on ferritin level and iron
panel.
Technical Approach: In this descriptive study a database containing demographic and medical
information will be constructed for patients who have anemia requiring non-emergent packed red
blood cell transfusions. Candidates for the study will be identified by a list of excluding medical
conditions a physician will go through prior to the transfusion and consent. Eligible patients who
consent to the study will have their iron panel and ferritin levels drawn prior to transfusion and
six other times as specified after transfusion.
Progress: This protocol remains ongoing at MAMC, with four out of five subjects completing the
required lab work. One subject died prior to completing the lab work; this death was unrelated to
study participation. Due to time constraints, enrollment has been on hold, but investigators plan
to resume enrollment during FY07.
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Detail Summary Sheet
Date: 30 Sep 06 Number: 205123 Status: Ongoing
Title: Current Use and Complications of Peripherally Inserted Central Catheters (PICC): A
Retrospective Study
Principal Investigator: CPT Kathleen C. Bauler, MC
Department: Medicine/Internal Medicine Facility: MAMC
Associate Investigator(s): CPT Joel T. Abbott, MC; MAJ Alexander S. Niven, MC; MAJ Cecily
K. Peterson, MC
Start - Completion: Funding: Periodic Review:
8/18/2005 - Jun 2006 DCI 9/21/2006
Study Objective: Evaluate the indications for placement, duration of therapy and complications
of peripherally inserted central catheters (PICC) lines in the inpatient population at Madigan
Army Medical Center.
Technical Approach: This is a retrospective chart review of consecutive inpatients with PICC
lines as identified from PICC service records. Subjects without documentation of a minimum of one
endpoint will be excluded from further analysis and recorded by clinical service as "no data
available." A data sheet will be completed for subjects with a minimum of one recorded end point
(PICC line placement, removal or "unknown" re: PICC). Each subject's demographics, pertinent
medical history, indication, duration, and complications of PICC line placement, nurse placing
PICC line and years of experience will be recorded. 100 consecutive subject's charts will be
reviewed using this criterion. Primary variables will be indication, duration of therapy, and
complications. Subjects with and without complications will be separated and analyzed by
indication, duration of therapy, demographic and medical information, and nursing information.
Data will be analyzed using Chi-squared, ANOVA and MANOVA analysis.
Progress: This retrospective review protocol continues to collect patient information. Several
patient charts selected were found not to have had PICC lines placed; rather patients had other
central lines placed. The PI has discussed other means of collecting data on patients with PICC
lines. At this time, 25 patients out of nearly 70 reviewed have been eligible for analysis.
202
Detail Summary Sheet
Date: 30 Sep 06 Number: 205039
Status: Ongoing
Title: Management of Parapneumonic Effusions: Does Following Pneumonia Treatment
Guidelines Affect Outcome? A Retrospective Study
Principal Investigator: CPT Patricia J. Dehaan, MC
Department: Medicine/Internal Medicine
Facility: MAMC
Associate Investigator(s): COL Bernard J. Roth, MC; John G. Meyer, MD
Rinard, MC
; MAJ John P.
Start - Completion: Funding:
2/11/2005 -Aug 2005 DCI
Periodic Review:
1/12/2006
Study Objective: To determine whether pneumonia treatment guidelines are being followed at
Madigan Army Medical Center in managing parapneumonic effusion and whether outcome is
affected via retrospective chart review.
Technical Approach: This is a retrospective study of parapneumonic effusions in patients with
the diagnosis of community-acquired pneumonia (CAP). Adult patients (age 18 years and older)
that meet the diagnosis of pneumonia will be studied to determine whether a parapneumonic
effusion (PPE) was present at time of diagnosis and if pneumonia management guidelines
published by the IDSA and ATS were followed. If a PPE was present on chest radiograph, was a
lateral decubitus study or CT scan then done? If the PPE layered >10 mm on lateral decubitus
radiograph, was thoracentesis done? Did it change patient management and was outcome affected?
If no difference of outcome is found, should the pneumonia management guidelines be updated?
This study will look at patients given the diagnosis of CAP during the time frame from 01 Jan 02
to 31 Dec 03.
Progress: This protocol remains ongoing. Data collection is complete but investigators are
compiling the findings for publication in a medical journal.
203
Detail Summary Sheet
Date: 30 Sep 06 Number: 206119 Status: Ongoing
Title: Urinary Markers of Renal Injury and N- Acetylcysteine Efficacy (URINE)
Principal Investigator: CPT Nathan R. Evans, MC
Department: Medicine/Internal Medicine Facility: MAMC
Associate Investigator(s): COL Howard M. Cushner, MC; MAJ Jason L. Davis, MC; CPT
Mehdi C. Shelhamer, MC
Start - Completion: Funding: Periodic Review:
10/18/2006 - Mar 2007 DCI N/A
Study Objective: The objective of this study is to attempt to measure NAC's effect at the renal
tubular cell level by measuring two known markers for renal cell injury after a contrast load. A
secondary objective will be to look into differences in these urinary enzyme levels based on how
much IV contrast volume was given in both the study and control groups.
Technical Approach: Up to 90 patients who have been scheduled for a radiologic imaging study
with IV contrast or heart catheterization will be recruited for this study. An additional 45 patients
scheduled for a non-invasive imaging study such as an ultrasound will also be recruited. The goal
is to enroll 135 patients who complete the study. Patients will be stratified by age (<50 and >50)
and creatinine clearance (60-90 versus >90) as calculated by the MDRD equation20 using a
completed chem 7 or 14. The patients undergoing a heart catheterization or IV radiologic imaging
study will be randomized to either NAC or no NAC using a computer program based on random
number generation. NAC will be administered in 4 ounces of orange juice and control patients will
receive an equivalent volume of normal saline (as NAC), also in 4 ounces of orange juice. Patients
will be blinded to treatment and questioned as to which treatment they believe they received after
the first dose and at the end of the study. 45 patients will be enrolled in a study group receiving
NAC prophylaxis for their contrast study. 45 patients will serve in a control group, which will not
receive NAC. The study will remain open until 45 patients are enrolled in each group. GGT and
NAG will be measured from urine collections prior to the administration of NAC and contrast and
24 hours after the administration of contrast. A 50 cc spot urine specimen will be collected on all
patients prior to taking the first dose of NAC. A second 50 cc spot urine specimen will then be
collected 24 hours after the contrast study. Both urine specimens will be used to measure urine
GGT and NAG levels standardized per gram of urine creatinine. The age, race, sex, baseline
MDRD GFR, presence of diabetes, use of ACE inhibitor and amount of IV contrast volume given to
each patient will also be recorded. Only the IND pharmacist will be aware of whether NAC is
given to the patient (via computer generated randomization). Patients and investigators will be
blinded as to who will receive NAC.
Progress: This greater than minimal risk protocol received initial approval with stipulations
during the convened IRB meeting on 22 August 2006. Final approval was granted 18 October
2006.
204
Detail Summary Sheet
Date: 30 Sep 06 Number: 206064
Status: Completed
Title: Does Participation in a Subspecialty Elective Rotation Improve the Respective American
Board of Internal Medicine Subspecialty Score?
Principal Investigator: CPT Collin J. Fischer, MC
Department: Medicine/Internal Medicine
Facility: MAMC
Associate Investigator(s): MAJ Cecily K. Peterson, MC;
CPT James A. Watts, MC
Start - Completion: Funding:
3/6/2006 - May 2006 DCI
Periodic Review:
N/A
Study Objective: (1) To determine if internal medicine resident participation in a one month
internal medicine subspecialty elective significantly affects the score of that particular
subspecialty on the American Board of Internal Medicine (ABIM) Certification Examination. (2)
To determine if internal medicine resident participation in all eight core internal medicine
subspecialty elective rotations (i.e. cardiology, pulmonary medicine, gastroenterology, nephrology,
infectious disease, rheumatology, hematology/oncology and endocrinology) confers a benefit as
measured by the overall ABIM Certification Examination score when compared to residents who
did not participate in all eight core internal medicine sub specialty elective rotations during
residency training. (3) To determine if internal medicine resident participation in four months or
more of "non medicine" electives during residency training is prognostic of a significantly worse
overall score on the ABIM.
Technical Approach: The specific subspecialty clinical rotations, ABIM Certifying Examination
(ABIMCE) total and subspecialty scores/deciles, and PGY-2 In Training Examination (ITE) total
score will be collected for each subject. Information on which subspecialty clinical rotations were
completed will be obtained from an examination of clinical evaluation forms completed at the end
of each clinical rotation. (1) Participants will be grouped within each subspecialty according to
number of months they spent performing that subspecialty elective during their PGY 2 and 3 years
(0, 1 and >1 months). Subjects will be paired according to their PGY-2 ITE percentile by year
score. ABIM subspecialty scores will be compared for statistically significant differences between
groups with the ANOVA test. (2) Subjects will be divided into 2 groups based on completion of the
entire set of 8 internal medicine "core electives" (defined above) versus non-completion. Subjects
will then be paired according to PGY-2 ITE percentile by year score. Total ABIMCE scores will be
compared for statistically significant differences between groups with a 2 tailed Student's t-test.
(3) The number of "non-medicine" electives will be tallied for each subject. A "non-medicine"
elective will be defined as any elective on which the preponderance of time is spent on a subject not
tested on the ABIMCE. Subjects will then be split into groups based on participation in <4 or >4
"non-medicine" elective months during residency, and paired according to their PGY-2 ITE
percentile score. Total ABIMCE scores will be compared for statistically significant differences
between groups with a 2 tailed Student's t-test.
Progress: This protocol was reported completed in July 2006. Results: Mean In- Training
Examination scores during the PGY-2 year was 64th percentile. The average ABIMCE overall
decile for the group was 7.2. The group had a 97% first time pass rate on the ABIMCE. Overall,
performing one or more months on a medicine subspecialty elective did not correlate with higher
sub-score for that speciality. In addition, completing the 'core' 8 medicine subspecialty elective
rotations during residency did not predict a significantly better overall score on the ABIMCE.
However, performing more non-medicine related electives was correlated with a significantly
worse overall score on the ABIMCE. The cut-off for this significance is 4 or more non-medicine
rounds.
205
Conclusions: Obtaining ABIM certification is an expected goal of Internal Medicine graduates and
residency programs. However, the ABIMCE is only validated to assess the medical knowledge
competency. Furthermore, for any individual, subspecialty sub-scores on the ABIMCE are only
important when one does not achieve certification on the first attempt. Hence, the factors that
drive subspecialty elective choice by residents (or requirements by programs) must include other
issues including demonstrating all the core competencies in that subspecialty discipline.
What our data does support is that even in this population skewed toward above average success
on the ABIMCE, increased numbers of non-medicine electives correlated with poorer overall
performance. At a micro level, this finding may influence program limitation on non-medicine
electives in residents at risk for not passing the ABIMCE on the first attempt. At a macro level,
this data is important to the academic Internal Medicine community as restructuring residency
training is being considered nationally.
206
Detail Summary Sheet
Date: 30 Sep 06 Number: 205104
Status: Completed
Title: Appropriate Use of CTPA in the Evaluation of Pulmonary Embolism
Hospital-Wide Referral Practices
- An Examination of
Principal Investigator: CPT Cristin A. Kiley, MC
Department: Medicine/Internal Medicine
Facility: MAMC
Associate Investigator(s): MAJ Vincent Mysliwiec, MC; MAJ Kristie J. Lowry, MC
Start - Completion: Funding:
7/12/2005 - Jul 2006 DCI
Periodic Review:
N/A
Study Objective: The primary objective of this study is to ascertain the physician ordering
practices for CT Pulmonary Angiography (CTPA) in the context of diagnosing pulmonary embolism
(PE) and to determine if these ordering practices meet accepted community standards.
Technical Approach: Patients who fit the initial study population will have their charts
reviewed by the investigators who will determine their modified Well's score for probability of
pulmonary embolism: i.e., the presence of a d- Dimer assay will be noted along with its result, EKG
and CXR findings, symptoms upon presentation, the result of the CTPA and documentation pre¬
test and post-test will all be reviewed. Based on accepted guidelines, a determination will be made
if the study was ordered appropriately. The percentage of CTPAs with positive findings will be
calculated and correlated with the number of studies to determine if MAMC ordering practices
meet community standards. Both pre and post test documentation concerning follow-up for
incidental abnormalities found on CTPA will be examined. If the data gathered suggest that
MAMC providers are ordering CTPAs inappropriately compared with community standards, a
proposal for initiating referral guidelines for CTPA to rule out PE in the MAMC health care
system will be put forth.
Progress: This protocol was reported completed in June 2006. Results: Of 394 charts reviewed,
303 patients underwent CTPA imaging and were included in further analysis. A Simplified Wells
score was calculated in 279 (92%) subjects, with a mean score of 1.6 + 1.6. 145 subjects had D-
dimers performed, of which 128 (88%) were positive. 20 CTPA were positive for VTE, a positive
rate of 7.2%. No subjects had a negative D-dimer and a positive CTPA. Follow-up imaging was
recommended in 145 (52%) of cases. Conclusion: This study demonstrated a statistically significant
lower rate of CTPA positivity. The expected positive rate for MAMC was 16%, the actual rate was
7.2% (p=.0004). Additionally, the sensitivity of the D-dimer was 100% with a specificity of 22%.
This is a result of failure to adhere to a validated clinical algorithm to assess for VTE and a large
proportion of low clinical probability patients.
207
Detail Summary Sheet
Date: 30 Sep 06 Number: 206087 Status: Ongoing
Title: Hemoptysis in Young Adults
Principal Investigator: CPT Herbert P. Kwon, MC
Department: Medicine/Internal Medicine Facility: MAMC
Associate Investigator(s): MAJ Vincent Mysliwiec, MC
Start - Completion: Funding: Periodic Review:
5/8/2006 - Aug 2006 DCI N/A
Study Objective: To report in case series format the causes of hemoptysis in young adults as
determined by bronchoscopy at the MAMC Pulmonary clinic in a retrospective medical record
review.
Technical Approach: A retrospective chart review will be performed utilizing the MAMC
Pulmonary Clinic Bronchoscopy logbook as the initial source of patient identification. The logbook
for the years of 2000-2006 will be screened for individuals undergoing bronchoscopy within the age
range of 18 through 45 years of age. The indication for bronchoscopy will be screened for
hemoptysis.
Progress: Nineteen subject's records were identified for inclusion in this retrospective review
protocol during FY06. The results collected so far will be presented at Army ACP, November 2006
in Washington D.C. The protocol remains ongoing at MAMC.
208
Detail Summary Sheet
Date: 30 Sep 06 Number: 206069 Status: Ongoing
Title: The Effects of Nighttime Low Dose Aspirin on Ambulatory Blood Pressure Testing in
Treated Hypertensive Patients
Principal Investigator: CPT Herbert P. Kwon, MC
Department: Medicine/Internal Medicine Facility: MAMC
Associate Investigator(s): MAJ Jason L. Davis, MC
Start - Completion: Funding: Periodic Review:
6/12/2006 - Dec 2006 DCI via Spacelabs N/A
Study Objective: To determine the benefits of aspirin chronotherapy in patients already on anti¬
hypertensive therapy.
Technical Approach: Eligible patients who consent to participate will have a baseline physical
exam performed that will include a cardiovascular exam. If signify underlying occult organic heart
disease is detected the patient will not be included in the study. If the work up is negative, the
patient will be included in the study. After an evening of fasting, patients will have six blood
pressure measurements taken after sitting for at least 5 minutes. All efforts will be made to
ensure the measurements are taken on the same type of machine by the same individual, and at
the relatively same times in the morning (between 0800 and 1100). Patients will be randomly
assigned to either remain on their aspirin in the morning or to take it nightly. Patients will then
have physical measurements taken and their fasting blood drawn. Finally, a Spacelabs 90207
Ambulatory Blood Pressure Monitor {ABPMj (Issaquah, Washington) will be placed and
instructions for use given.
Ambulatory Blood Pressure Monitor: Patients will have blood pressure and heart rates measured
every 20 minutes between 0700 and 2300 if they are civilian and 0600 and 2200 if they military
participants. During the eight hour "rest period" patients will have measurements taken every 30
minutes. Data will not be used if there is >30% of measurements missing, data missing for more
than 2 hours, or if patients fail to return for a second ambulatory blood pressure measurement.
After returning the blood pressure monitor, patients will receive a new bottle of aspirin with a
sticker stating if the medication should be taken in the morning or evening in addition to the
normal written instructions, which will conclude initial randomization to a study arm.
Investigators will be blinded to the timing of aspirin administration. Measurements will be
submitted via email at Months 0-3 (First Inter-measurement Period), Month 3 (Interim
Evaluation) and Months 4-6 (Second Inter-measurement Period. Patients will have the timing of
their low dose aspirin reversed, serving as their own controls and cross-overs. Participants who
took it in the evening will now take it in the morning and vice versa. Patients will be contacted,
encouraged to stay consistent with the protocol, and/or to contact Dr. Kwon or study staff. The
values obtained for the ABPM and the fasting labs at the interim evaluation above will be used
also for the baseline for the second inter-measurement period.
Final Evaluation: After the final three months of therapy patients will return for a fasting
laboratory sampling, appointment and re-measurement of blood pressure to include another 48
hour AMBP. Medical records will be reviewed for any interim visits, hospitalizations, or
medication changes. Patients will be asked if they suffered any increase in side effects or
gastrointestinal discomfort during the study period.
Progress: This study was delayed for five months prior to enrolling patients. Three months
following initial IRB review, the Department of Nursing made multiple reviews of the study prior
to releasing their impact statement in support of this study. It was further delayed for two months
209
when Clinical Engineering stated that the necessary equipment could not be held or utilized at the
hospital for the allotted timeframe of the study. After a lengthy debate and review of the
CRADA/SOW, Clinical Engineering approved the equipment for use at MAMC. No subjects
enrolled during FY06.
210
Detail Summary Sheet
Date: 30 Sep 06 Number: 205038 Status: Terminated
Title: Effect of A Single Intra-articular Steroid Injection on Serum Fructosamine Levels in
Patients with Type 2 Diabetes Mellitus
Principal Investigator: CPT George R. Mount, MC
Department: Medicine/Internal Medicine Facility: MAMC
Associate Investigator(s): CPT Cristin A. Kiley, MC; MAJ Brian T. McKinley, MC; CPT Kyle
C. Harner, MC
Start - Completion: Funding: Periodic Review:
2/3/2005 - Jan 2006 DCI N/A
Study Objective: The primary objective of this study is to observe the effect that a single dose of
corticosteroid (40mg kenalog, lcc) injected into the knee joint has on the serum glucose level in
individuals with type 2 diabetes mellitus.
Technical Approach: Subjects presenting to the Rheumatology clinic for intra-articular steroid
injection into the knee, who have Diabetes Mellitus and are not currently taking insulin therapy
will be deemed eligible for the study. Subjusts who meet the criteria will offered consented. If they
do wish to participate, the consent form will be signed and the patient will receive their joint
injection. Subjects will report to the lab immediately after joint injection for Fructosamine level
and HbAlc. Subjects will return to the lab in two weeks for Fructosamine level. Subjects will
return to the lab in two weeks (4 weeks from time of injection) for Fructsamine level and HbAlc.
Subject participation will be complete at this time. Lab results will be gathered by the
investigators and the data will be analyzed.
Progress: This protocol was terminated by investigators in June 2006 due to a lack of accrual.
211
Detail Summary Sheet
Date: 30 Sep 06 Number: 202048 Status: Ongoing
Title: A Multinational, Randomized, Double-blind, Placebo-controlled, Forced-titration, 2X2
Factorial Design Study of the Efficacy and Safety of Long Term Administration of Nateglinide
and Valsartan in the Prevention of Diabetes and Cardiovascular Outcomes in Subjects with
Impaired Glucose Tolerance (IGT), Protocol No. CDJN608 B2302
Principal Investigator: MAJ Patricia A. Short, MC
Department: Medicine/Internal Medicine Facility: MAMC
Associate Investigator(s): LTC Jon C. Allison, MC; Marvin Y. Hayami, M.D.; MAJ Cecily K.
Peterson, MC; Shaila B. Kode, M.D.
Start - Completion: Funding: Periodic Review:
4/19/2002 - Aug 2009 Novartis via Henry M. Jackson Foundation 1/24/2006
Study Objective: Core Phase: to evaluate the effect of long-term administration of nateglinide
and valsartan on the progression to diabetes in subjects with impaired glucose tolerance (IGT) at
increased risk of a cardiovascular event. Extension Phase: to evaluate the effect of long-term
administration of nateglinide and valsartan on cardiovascular morbidity and mortality. Definition
of this composite endpoint is provided on page 11 of the attached Protocol, and is further discussed
in the Summary to this cover document.
Technical Approach: Approximately 24 subjects will be enrolled at MAMC. Study design
projects enrollment of 7500 subjects from 600-800 centers in about 40 countries, with
approximately 1875 subjects in each of 4 treatment groups. 75% of subjects will receive at least
one of the study drugs. All study drugs are taken orally. Patients will be invited to participate in
screening who have one or more risk factors for the conditions under study (such as family history,
known IGT, high BMI, dyslipidemia.) Eligible patients will be randomized into one of four groups
(1. Nateglinide 60 mg before meals + matching placebo once daily; 2. Nateglinide 60mg before
meals + Valsartan 160mg once daily; 3. Matching placebo before meals + matching placebo once
daily; 4. Matching placebo before meals + Valsartan 160mg once daily) using an electronic
interactive voice recognition system. There will be sixteen study visits after initiation of study
treatment: at +2 weeks, +4 weeks, +3 months, +6 months, then visits will be every 6 months.
Patients will arrive fasting, scheduled between 7- 10am. Weight, blood pressure, heart rate and
blood sampling is performed at each visit. A urine specimen will be collected at 3 time points. An
ECG, (electrocardiogram) is performed at the second visit and repeated twice during the study.
The OGTT with FPG and insulin level is completed every 12 months after baseline, at month
37(for confirmation), and as indicated to confirm progression to diabetes. Subjects are asked to
keep a diary of suspected hypoglycemic events and a subset of patients may be provided a blood
glucose monitor to record these occurrences. This study will include life style intervention
counseling of subjects at every visit, with written educational materials provided by the study
sponsor.
Progress: This protocol closed to patient entry 26 November 2003, with five subjects enrolled.
Three subjects continued to be followed at MAMC during FY06.
212
Detail Summary Sheet
Date: 30 Sep 06 Number: 204045 Status: Ongoing
Title: A Prospective, multinational, multicenter, double-blind, randomized, active-controlled
trial to compare the effects of Lotrel (amlodipine/benazepril) to benazepril and
hydrochlorothiazide combined on the reduction of cardiovascular morbidity and mortality in
patients with high risk hypertension, Protocol No. CCIB002I2301: ACCOMPLISH (Avoiding
Cardiovascular Events through COMbination Therapy in Patients Living with Systolic
Hypertension)
Principal Investigator: MAJ Patricia A. Short, MC
Department: Medicine/Internal Medicine
Facility: MAMC
Associate Investigator(s): LTC Jon C. Allison, MC; Michael R. Voorhies, PAC
Start - Completion: Funding:
4/7/2004 - Oct 2009 SWOG via Henry M. Jackson Foundation
Periodic Review:
1/24/2006
Study Objective: (1) To assess the time to first event of composite cardiovascular morbidity and
mortality with amlodipine/benazepril (Lotrel®) compared with the combination of benazepril and
hydrochlorothiazide in patients with high risk hypertension. (2) To compare composite
cardiovascular morbidity, new onset diabetes, progression of renal disease and hospitalization for
congestive heart failure with amlodipine/benazepril (Lotrel®)versus the combination of benazepril
and hydrochlorothiazide. (3) to compare all-cause mortality, all hospitalizations, renal function
(estimated change in glomerular filtration rate), LVH, peripheral arterial revascularization
procedure or nontraumatic amputation and progression/regression of microalbuminuria (30-300
mg/g) or clinical albuminuria (>300 mg/g) long term safety and tolerability with
amlodipine/benazepril (Lotrel®) versus the combination of benazepril and hydrochlorothiazide. (4)
To identify inherited genetic factors which may be related to hypertension, predict response to
treatment with the study medications, predict relative susceptibility to drug-drug interactions, or
predict genetic predisposition to serious side effects.
Technical Approach: This is a phase III randomized, multicenter, double-blind, parallel-group,
active-controlled trial comparing the efficacy of amlodipine/benazepril combined therapy (Lotrel) to
the combination of benazepril and hydrochlorothiazide (HCTZ) in high risk hypertensive subjects
in reducing cardiovascular outcomes. 20 subjects may be enrolled at MAMC with approximately
12,600 worldwide. The study will last approximately 5 years, including the 18-month recruitment
period. Eligible subjects will be randomized in 1:1 ratio to one of two groups to begin blinded
treatment with amlodipine/benazepril 5/20 mg or benazepril 20mg/HCTZ 12.5 mg. The study
provides for dose-titration followed by add-on therapy if necessary to achieve goal blood pressure
(<140/<90 mmHg or lower in appropriate subjects).
Subjects will be followed every 4 weeks up to 3 months, at 6 months, and every 6 months
thereafter. All randomized subjects will be followed until study completion, including those who
interrupt or discontinue treatment. Additional visits may be done as needed to ensure blood
pressure control. Patients will be treated in the study until the required number of randomized
subjects with a primary cardiovascular event is achieved for analysis. Safety and efficacy
assessments will consist of monitoring pre-defined non-serious adverse events, all serious adverse
events, concomitant medications, regular monitoring of hematology and blood chemistry,
urinalysis, vital signs and physical examinations. Observation for clinical endpoints will be
continuous. Physical exams will focus on cardiovascular signs and symptoms. 12-lead ECG will be
performed at baseline, month 18 and year 3. 24-hour ambulatory blood pressure monitoring at
Year 2 will be done in a subset of subjects. Biomarker tests for high sensitivity C-reactive protein
and other predictors of cardiovascular disease are scheduled. Subject participation in a
pharmacogenetics sub-study is optional. A single blood specimen will be collected and DNA derived
213
from the sample may be stored and studied for up to 20 years by the study sponsor. Interim
analyses for monitoring of efficacy demonstration and patient safety will be conducted by an
independent Data Monitoring Committee.
Progress: This protocol closed to enrollment with 28 patients consented, 17 enrolled. Three
subjects have discontinued taking study medication and all 17 continued to be followed during
FY06.
214
Detail Summary Sheet
Date: 30 Sep 06 Number: 205004
Status: Completed
Title: Efficacy of Iron in Restless Legs Syndrome (RLS) Patients With Low-Normal Ferritin: A
Randomized, Double-Blind, Placebo Controlled Study
Principal Investigator: CPT Jam7es Y. Wang, MC
Department: Medicine/Internal Medicine
Facility: MAMC
Associate Investigator(s): MAJ Angela G. Mysliwiec, MC;
CPT Collin J. Fischer, MC
Start - Completion: Funding:
1/31/2005 - Aug 2005 DCI
Periodic Review:
10/25/2005
Study Objective: To determine the efficacy of treating RLS patients who have low-normal
ferritin with oral ferrous sulfate.
Technical Approach: This is a double blinded placebo-controlled study of iron in RLS patients
that have a low-normal ferritin level (12-100mcg/l). Adult patients (age > 18) that meet the
International RLS Study group diagnostic criteria for RLS will be consented to have a ferritin, iron
panel, and CBC checked. Those who have concurrent ferritin in the low-normal range (12-100mg/l)
and at least moderately severe symptoms according to the IRLSSG rating scale for RLS will be
eligible for the study. Sample size will be between 9-39 patients in each treatment group for a total
of 18-78 patients. These patients will be randomized to treatment with 325mg iron twice a day by
mouth or placebo. Patients will have follow up at 6 and 12 weeks post treatment. Outcome will be
measured by improvement in overall score(decrease in total score by least 5 points) on the IRLSSG
RLS validated severity survey from pre-treatment to 12 weeks post treatment and a statistical
improvement of treatment group vs. placebo using the T test for independent samples. An
additional endpoint measurement will be overall improvement in quality of life after treatment.
Patients will be treated for a total of 12 weeks in this trial.
Progress: This protocol was reported completed in June 2006, with 38 subjects consented.
Seventeen subjects completed the study, two left the area before completing, one did not think iron
would benefit him, and eighteen screen-failed. No patients had significant adverse side effects
from the study medication. Preliminary data analysis suggests that treating RLS patients with
low- normal ferritin with PO iron may improve RLS symptoms and overall quality of life.
215
Detail Summary Sheets
Nephrology Service, Department of Medicine
216
Detail Summary Sheet
Date: 30 Sep 06 Number: 205121
Status: Completed
Title: Does High Resistive Index by Doppler Ultrasonography Predict Small Kidney Sizes?
Principal Investigator: MAJ Joseph Y. Lee, MC
Department: Medicine/Nephrology
Facility: MAMC
Associate Investigator(s): CPT David Owshalimpur, MC
Start - Completion: Funding:
8/18/2005 - Dec 2005 DCI
Periodic Review:
N/A
Study Objective: To retrospectively determine if high resistive indices by Doppler
ultrasonography is predictive of small kidney sizes.
Technical Approach: This study is a retrospective review and data analysis of up to 400 Doppler
ultrasound reports in the Vascular Clinic Lab database. Data recorded will include age, sex,
percentage of renal artery stenosis (as reflected by aorta/renal artery velocity ratios), resistive
index and kidney sizes. A review of ICDB medical records will be done to exclude the reports from
patients who have a single kidney, diabetes, or infiltrative/cystic kidney disease. The control group
will be ultrasound reports of patients who have no significant renal artery stenosis (>60%) or high
resistive index (>80%). The resistive indices and kidney sizes will be grouped by age into this
range: <30, 31-60, and >60. The control group will be divided the same way. Descriptive statistics
will be used to summarize the overall sample. A correlation coefficient will be used to compare
high resistive index to kidney size. Student's T-test will be used to compare mean kidney size of
those with and without renal artery stenosis. A regression analysis will be used to determine the
influence of resistive index, age, serum creatinine, GFR, and renal artery stenosis on kidney size.
Progress: This protocol was reported completed in April 2006. Results: There was no correlation
between high renal resistive index and kidney size; nor any correlation between age, serum
creatinine and male gender with kidney size. Both advancing age and serum creatinine were found
to have smaller kidneys, while male gender compared to female gender had larger kidneys.
Conclusion: This retrospective study did not show a correlation between renal resistive index, an
indirect measure of small vessel kidney disease presumed to be caused by kidney sclerosis and
kidney size.
217
Detail Summary Sheets
Neurology Service, Department of Medicine
218
Detail Summary Sheet
Date: 30 Sep 06
Number: 204062
Status: Ongoing
Title: A Randomized Trial of a Migraine Management Seminar
Principal Investigator: MAJ Jay C. Erickson, MC
in the Treatment of Migraines
Department: Medicine/Neurology
Facility: MAMC
Associate Investigator(s): COL Beverly R. Scott, MC; Joan L. Wilson, MSW; CPT Douglas R.
Langford, MC
Start - Completion:
4/15/2004 - Mar 2006
Funding:
DCI
Periodic Review:
3/28/2006
Study Objective: To determinie the effectiveness of a migraine management seminar for
improving migraine headaches, migraine-associated disability and migraine-related quality of life.
Technical Approach: Subjects will attend a unique, 3-hour, single-session seminar to augment
the medical management of migraine headaches. The seminar will educate subjects with
migraines about their disorder and various treatments and teach practical non-pharmacologic
migraine management skills. The study is a randomized, controlled, single-center trial to
determine the efficacy of a migraine management seminar, when used as adjunctive therapy to
standard medical therapy in the treatment of migraine headaches. Eighty subjects, fulfilling the
International Headache Society criteria for migraines and suffering from significant migraine
associated disability will be enrolled in the study. Subjects will be recruited from consecutive
subjects referred to the MAMC Neurology Clinic for headache consultation. Study subjects will be
randomized to medical therapy (control group) or medical therapy in combination with the
migraine management seminar (treatment group). Medical therapy will be determined by each
subject's consulting neurologist, will conform to standard of care for the treatment of migraine and
not be constrained or otherwise influenced by the study. All subjects will record a standardized
headache diary during the study period. The primary outcome measures are number of headache
days per month and change in the Migraine Disability Assessment (MIDAS) score. Secondary
outcomes include the Migraine Specific Quality of Life (MSQOL) questionnaire score, migraine
severity and duration, healthcare utilization and a migraine management satisfaction survey.
Outcomes will be assessed at baseline, 3 months after randomization and 6 months after
randomization.
Progress: This protocol is open to enrollment 52 patients enrolled at MAMC. Twenty-six (26)
patients have completed the study, seventeen remain actively enrolled, and nine were lost to
follow-up. There have been no adverse outcomes. No data analysis has been done.
219
Detail Summary Sheet
Date: 30 Sep 06 Number: 203048
Status: Ongoing
Title: A Randomized Trial of B Vitamins for Alzheimer's Disease
Principal Investigator: MAJ Jay C. Erickson, MC
Department: Medicine/Neurology
Facility: MAMC
Associate Investigator(s): COL Frederick G. Flynn, MC
Start - Completion: Funding:
6/8/2004 - Mar 2005 Upsher-Smith Laboratories via Henry M.
Jackson Foundation
Periodic Review:
1/24/2006
Study Objective: To determine whether B vitamin supplements improve cognitive function in
patients with mild-to-moderate Alzheimer's disease.
Technical Approach: To test the hypothesis that B vitamin supplements improve cognitive
function in patients with Alzheimer's disease, 80 patients with mild-to-moderate Alzheimer's
disease will be enrolled in a prospective, randomized, open-label trial. Subjects will be randomized
to receive B vitamin supplements consisting of vitamin B12 (0.5 mg qd), vitamin B6 (50 mg qd),
and folate (2 mg qd) or no B vitamin supplements over a period of 1 year. Cognitive function, as
measured by the Alzheimer's Disease Assessment Scale (ADAS), will be measured at baseline and
then after 3 months, 6 months, and 12 months of treatment. The primary outcome will be change
in ADAS score compared to baseline. Analysis of variance will be used to test for significant
differences between the two treatment groups.
Progress: This protocol remains open to enrollment, with six subjects enrolled, one during FY06.
Five subjects have completed participation, and one subject continued to be followed. No adverse
events have occurred.
220
Detail Summary Sheet
Date: 30 Sep 06 Number: 206075 Status: Ongoing
Title: Association Between Migraine and Psychiatric Conditions In Soldiers Returning from
Combat
Principal Investigator: MAJ Jay C. Erickson, MC
Department: Medicine/Neurology Facility: MAMC
Associate Investigator(s): COL Gregory A. Gahm, MS; Barbara A. Lucenko, PhD;
Start - Completion: Funding: Periodic Review:
4/4/2006 - Dec 2006 DCI N/A
Study Objective: Objectives: To determine the prevalence of post-traumatic stress disorder
(PTSD) among Soldiers with and without migraine headaches, to determine the prevalence of
depression among Soldiers with and without migraine headaches, to determine the association
between PTSD and migraine outcomes in Soldiers, and to determine the association between
depression and migraine outcomes in Soldiers.
Technical Approach: PHQ-9 and PC-PTSD scores will be obtained from the SWAP database for
each subject enrolled in the migraine screening database. A single database will be constructed.
Progress: This protocol is closed to patient entry, with a total of 2,605 subjects enrolled in this
cross-sectional, observational study. The protocol remains ongoing for data analysis.
221
Detail Summary Sheet
Date: 30 Sep 06 Number: 203097 Status: Ongoing
Title: CLOSURE I Trial: A Prospective, Multicenter, Randomized, Controlled Trial to Evaluate
the Safety and Efficacy of the STARFlex Septal Closure System Versus Best Medical Therapy in
Patients with a Stroke and/or Transient Ischemic Attack Due to a Presumed Paradoxical
Embolism Through a Patent Foramen Ovale
Principal Investigator: MAJ Jay C. Erickson, MC
Department: Medicine/Neurology
Facility: MAMC
Associate Investigator(s): COL Beverly R. Scott, MC; COL David T. Schachter, MC; CPT Erek
K. Helseth, MC
Start - Completion: Funding:
9/18/2003 - Oct 2006 NMT Medical, Inc via Henry M. Jackson
Foundation
Periodic Review:
6/27/2006
Study Objective: To determine whether the STARFlex Septal Closure System (STARFlex) will
safely and effectively prevent recurrent embolic stroke/transient ischemic attack (TIA) and
mortality in patients with a patent foramen ovale (PFO) and to demonstrate superiority of the
STARFlex device compared to best medical therapy.
Technical Approach: The STARFlex Septal Closure System is an investigational device for non-
surgical, transcatheter closure of intracardiac defects. The CLOSURE I Trial is a prospective,
multicenter, randomized, controlled trial to evaluate the safety and efficacy of the STARFlex
System in preventing recurrent cerebrovascular events in patients with a PFO. The study will
enroll MAMC patients 18 to 60 years of age who have had a documented stroke or TIA within the
last 3 months, have a PFO as detected by transesophageal echocardiography (TEE) with saline
contrast bubble study, and do not have any other potentially embolic source or other cause of
stroke or TIA. Up to 15 patients will be enrolled at MAMC and a total of 1600 patients will be
enrolled at 120 centers in the United States. Investigators will receive training in use of the
device. Patients will be randomized to receive implantation of the STARFlex device with
concomitant aspirin therapy or medical therapy consisting of aspirin and/or coumadin. Patients
who have device implantation will also be treated with clopidogrel (Plavix) 75mg daily for 6
months. All patients will undergo serial physical exams, EKGs, and neurological evaluations (to
detect recurrent stroke or TIA) at 6 months, 12 months, and 24 months after device implantation
or initiation of medical therapy. Patients who receive the device will also have a transesophageal
echocardiogram with saline contrast bubble study and chest x-ray 6 months after implantation to
assess for closure of the PFO and condition of the device. The primary endpoints of the study are
the 2-year incidence of stroke/TIA and all cause mortality. Data will be analyzed on an intent-to-
treat basis using the chi-square test and logistic regression. A central Data and Safety Monitoring
Board will inspect and make recommendations regarding rate of stroke/TIA at approximately 10
months and 18 months after start of the study for efficacy or safety concerns.
Progress: This protocol remains open to enrollment with three volunteers enrolled in the last
twelve months, bringing the total number of enrolled subjects to eight. Four subjects were
randomized to the STARflex device arm and four subjects were randomized to the medical therapy
arm. Two subjects have moved away from the area and will complete study participation at
another research site. Six subjects continued to be followed at MAMC during FY06. The STARflex
device became dislodged in one subject during the implantation procedure, requiring surgical
removal, but there were no long-term complications.
222
Detail Summary Sheet
Date: 30 Sep 06 Number: 205107 Status: Completed
Title: Diagnosis and Treatment of Migraines in U.S. Army Soldiers
Principal Investigator: MAJ Jay C. Erickson, MC
Department: Medicine/Neurology Facility: MAMC
Associate Investigator(s): CPT Douglas R. Langford, MC
Start - Completion: Funding: Periodic Review:
7/21/2005 - Sep 2005 DCI N/A
Study Objective: (1) To determine the proportion of soldiers with migraines whose headaches are
diagnosed as migraines prior to neurology consultation. (2) To determine the prevalence of
analgesic overuse among soldiers with migraine. (3) To determine the medical treatment provided
to soldiers with migraines.
Technical Approach: A retrospective chart review will be performed to determine the patterns of
medical care provided to Army soldiers with migraine headaches. The charts of 50 consecutive
active duty Army soldiers meeting International Headache Society diagnostic criteria for migraine
headaches who were evaluated in the MAMC neurology clinic in 2004 will be reviewed. Diagnosis
and treatments prior to, and after, neurology consultation will be compared. Endpoints will include
the proportions of patients diagnosed with migraine, treated with prophylactic medications,
treated with triptan-class medications, and treated with non-pharmacologic treatments.
Progress: A total of 50 Soldiers participated. A diagnosis of migraine was made in 42% of patients
prior to neurology referral and in 100% upon neurology consultation (p<0.001). Analgesic overuse
was diagnosed in 0% of patients before neurology consultation and in 23% at the time of neurology
consultation (p<0.001). 63% of eligible patients were treated with a prophylactic medication prior
to neurology referral compared to 100% after neurology consultation (p<0.01). Prior to neurology
referral, acute migraine treatment using combination analgesics or opioids was significantly more
common (p<0.001) and treatment using a triptan medication was significantly less common
(p=0.003). Non-pharmacologic treatments for migraine were used in 4% of patients before
neurology referral and in 52% after neurology consultation.
Conclusions: Migraine headaches are frequently undiagnosed in Soldiers prior to neurology
consultation. Concomitant analgesic overuse affects nearly one quarter of Soldiers with migraines
at the time they are first seen in neurology, but is rarely recognized prior to referral. Soldiers with
migraines are less likely to be treated with prophylactic medication, migraine-specific medications,
or non-pharmacologic treatments prior to neurology consultation. Improving the ability of first-
line providers to diagnose and treat migraine will reduce the burden of this disorder in Soldiers
and thus enhance military readiness.
223
Detail Summary Sheet
Date: 30 Sep 06 Number: 205118 Status: Ongoing
Title: Prevalence and Impact of Migraine Among Deployed Soldiers
Principal Investigator: MAJ Jay C. Erickson, MC
Department: Medicine/Neurology Facility: MAMC
Associate Investigator(s): CPT Brett J. Theeler, MC
Start - Completion: Funding: Periodic Review:
8/5/2005 - Dec 2005 DCI 7/18/2006
Study Objective: (1) To determine the prevalence of migraine among soldiers during military
deployment. (2) To determine the frequency and severity of migraine headaches among deployed
soldiers. (3) To determine the impact of migraines on soldier readiness during deployment. (4) To
determine the diagnosis and treatment patterns of migraine among deployed soldiers.
Technical Approach: This is a cross-sectional, observational, questionnaire based study to
determine the prevalence, impact, and treatment patterns of migraine among soldiers during
military deployment. Approximately 3,000 soldiers of the 1st Stryker Brigade will be asked to
voluntarily complete a standardized, validated, headache questionnaire during their post¬
deployment health evaluation. The questions on the questionnaire are based on the diagnostic
criteria of migraine, headache frequency, headache-related disability, and headache treatments.
Responses will be used to calculate the prevalence, frequency, severity, and duration of migraines
among deployed soldiers. The extent to which migraines impede performance of military duties
and current treatment patterns for migraine among this population will also be determined.
Dependent variables include: proportion of soldiers experiencing one or more migraine headaches
during deployment; mean number of headache days per month; mean duration and severity of
headaches; number of missed and sub-optimal duty days attributable to headache; proportion of
soldiers with migraine who were previously diagnosed by a healthcare provider and proportion of
soldiers with migraine who used migraine -specific medications during deployment.
Progress: The study questionnaire was completed by 2,725 Soldiers; 377 Soldiers with migraines
subsequently completed a follow-up questionnaire three months later. Data analysis is almost
complete. Preliminary results were presented at the American Headache Society meeting 24 June
2006.
224
Detail Summary Sheet
Date: 30 Sep 06 Number: 205115 Status: Ongoing
Title: Study of Acute Viprinex™ for Emergency Stroke: A Randomized, Double-Blind, Placebo-
Controlled Study of Viprinex™ (Ancrod Injection) in Subjects Beginning Treatment within 6
Hours of the Onset of Acute, Ischemic Stroke
Principal Investigator: MAJ Jay C. Erickson, MC
Department: Medicine/Neurology Facility: MAMC
Associate Investigator(s): MAJ Robert B. Blankenship, MC; MAJ Anna D. Hohler, MC; CPT
Jessica D. Lee, MC; CPT Douglas R. Langford, MC; MAJ Jason A. Friedman, MC; CPT Erek K.
Helseth, MC; COL Beverly R. Scott, MC
Start - Completion: Funding: Periodic Review:
11/9/2005 - Sep 2007 Neurobiological Technologies, Inc. via Henry 7/20/2006
M. Jackson Foundation
Study Objective: To determine whether ancrod (Viprinex™) begun intravenously within 6 hours
of stroke onset confers statistically benefit in reducing the incidence of disability at 90 days
Technical Approach: This is a phase III, double-blind, placebo controlled study to that will be
conducted by the Neurology/Stroke Team service at MAMC. Up to 10 subjects may be enrolled; a
total of 500 enrolled in the study overall. Eligible subjects will present to the ER with the
diagnosis of a stroke and symptom onset within 6 hours before the Ancrod infusion. If patients are
eligible to receive rt-PA, they will not be enrolled in this study. Subjects will have a routine history
and physical, neurological examination, laboratory tests, a non-contrast CT scan, and a 12 lead
ECG. Subjects will be randomized to one of two treatment groups in a biased-coin approach using
study-wide balanced enrollment in the two treatment groups by age category (<65, 65-75, >75),
independent of stratum assignment. Randomization will be completed via an interactive voice
response system. Subjects will receive the 3 hour transfusion and continue to have follow-up after
discharge until 90 days after being treated with study medication.
Progress: This protocol remains open to patient entry. No patients have met enrollment criteria.
Study staff continues to actively screening all acute stroke patients.
225
Detail Summary Sheets
Pulmonary Disease & Critical Care Service,
Department of Medicine
226
Detail Summary Sheet
Date: 30 Sep 06 Number: 205032
Status: Terminated
Title: Adjunctive Role of Mirtazapine in Mild Positional Sleep Apnea
Principal Investigator: LTC (Ret) William E. Caras, M.D.
Department: Medicine/Pulmonary & Critical Care
Facility: MAMC
Associate Investigator(s): COL Bernard J. Roth, MC; MAJ Vincent Mysliwiec, MC; Larry G.
Knauss, Ph.D.
Start - Completion: Funding:
Periodic Review:
10/11/2005 - Nov 2005 Oraganon via The Geneva Loundation
1/18/2006
Study Objective: This study plans to look at the adjunctive role of Mirtazapine, an
antidepressant with sleep enhancing qualities, to positional therapy (PST) in patients with mild
positional OSA.
Technical Approach: This is a prospective randomized placebo controlled trial. 30 subjects will
be enrolled following screening and randomized to receive active drug or placebo. Both groups will
be asked to complete a sleep diary. PSG variables will be total sleep time, sleep efficiency, sleep
latency, Stage 1 sleep, Stage 2 (min) Stage 3(min), Rem (min), Rem latency (min). Amended: Jan
2006, to an open, sequential design to allow all potential patients to enroll in the 1st phase of the
study, which will use only the positional sleep vest. After a month of treatment patients will be
reassessed and then may chose to enroll in the 2nd phase of the study combining the sleep vest
with Mirtazapine.
Progress: This study was amended in January 2006, to an open, sequential design to allow all
potential patients to enroll in the first phase of the study using only the positional sleep vest. After
a month of treatment patients would be reassessed and then may chose to enroll in the second
phase of the study combining the sleep vest with Mirtazapine. However, Dr. Caras eventually
terminated the study due to lack of accrual citing patient's deep seated reluctance to take a
medication known as an antidepressant.
227
Detail Summary Sheet
Date: 30 Sep 06 Number: 206083 Status: Terminated
Title: A Randomized, Double-blind, Placebo-controlled, Parallel Group, Stratified, Multi-center,
12 Week Study Comparing the Safety and Efficacy of Fluticasone and Formoterol Combination
(FlutiForm™ 100/10 meg twice daily) in a Single Inhaler (SkyePharma HFA pMDI) with the
Administration of Placebo or Fluticasone (100 meg twice daily) and Formoterol (10 meg twice
daily) Alone in Adolescent and Adult Patients with Mild to Moderate Asthma
Principal Investigator: LTC Cynthia F. Clagett, MC
Department: Medicine/Pulmonary & Critical Care
Facility: MAMC
Associate Investigator(s): MAJ Alexander S. Niven, MC; CPT Katherine A. Simonson, AN
Start - Completion: Funding:
6/28/2006 - Dec 2007 SkyePharma via Henry M. Jackson
Foundation
Periodic Review:
N/A
Study Objective: The primary objective is to demonstrate the efficacy of SKP FlutiForm HFA
pMDI compared to Fluticasone propionate and Formoterol fumarate alone and placebo when
administered by inhalation twice daily over 12 weeks in adult patients with mild to moderate
asthma. (Only subjects 18 years or older with mild asthma will be enrolled at MAMC)
Technical Approach: All eligible patients will undergo a Run-In Period of up to 2 weeks
depending on their history of steroid use. Steroid-requiring patients will undergo a Run-In Period
up to 2 weeks during which they will receive asthma maintenance therapy using Fluticasone HFA
pMDI (50 meg twice daily). Steroid-free patients will undergo a Run-In Period up to 4 weeks
during which they will not receive any controlling medication. Use of rescue Albuterol pMDI will
be permitted for all patients as needed for the control of worsening asthma symptoms during the
Run-In period. At the Baseline Visit (Week 0) following the Run-In period, eligible patients will be
randomized to the treatment groups. Treatment assignment will be stratified according to prior
steroid use (steroid-requiring versus steroid free). Study drug will be administered twice daily over
a 12 week period. Patient visits will occur at Weeks 2, 4, 8 and 12, during which assessments
(including serial PFTs up to 4 hours) will be made. During the Treatment Period, patients may
take only their blinded study medication; all other asthma medications will be withheld for the
duration of the Treatment Period. Use of the rescue Albuterol pMDI will be permitted in all
patients as needed during the Treatment Period for control of worsening asthma symptoms.
Progress: This protocol was terminated 21 September 2006, due to failed contract negotiations
with the study sponsor. The study was never initiated at MAMC.
228
Detail Summary Sheet
Date: 30 Sep 06 Number: 206086 Status: Ongoing
Title: Identifying Adherence Obstacles to CPAP Therapy
Principal Investigator: MAJ Vincent Mysliwiec, MC
Department: Medicine/Pulmonary & Critical Care Facility: MAMC
Associate Investigator(s): Robert D. Swanson, M.A.; Suzette Gagnon-Bailey, RN; Michael J.
Kuculyn; Richard D. Guesford
Start - Completion: Funding: Periodic Review:
5/8/2006 - Aug 2007 DCI N/A
Study Objective: The primary objective of this study is to introduce a survey, in the form of a
Concerns Questionnaire that will assess compliance and reasons for non-compliance in patients
diagnosed with Obstructive Sleep Apnea (OSA) who are prescribed Continuous positive airway
pressure (CPAP).
Technical Approach: Subjects with OSA that will be treated with CPAP will be identified by
treating provider and scheduled for follow up within 3 months. Subjects will return for follow up
with the downloaded data from CPAP machine and compliance data downloaded. During this time
patients will complete the "PAP Concerns Questionnaire." The downloaded data are transferred to
"CPAP Concerns Questionnaire" for analysis.
Progress: Data collection is complete with 100 patients who utilize CPAP having filled out the
questionnaire during FY06. Data has been entered into a excel spread sheet and is ready for
interim analysis. At this point we plan to identify which specific questions are statistically
significant in determining CPAP compliance.
229
Detail Summary Sheet
Date: 30 Sep 06 Number: 205128 Status: Ongoing
Title: Impulse Oscillometry and Obstructive Lung Disease: Assessment of a Clinically
Significant Bronchodilator Response
Principal Investigator: MAJ Alexander S. Niven, MC
Department: Medicine/Pulmonary & Critical Care Facility: MAMC
Associate Investigator(s): MAJ Steven P. Bennett, MC; LTC Cynthia L. Clagett, MC; CPT
Johathan R. Coyle, MC; Suzette Gagnon-Bailey, RN; MAJ William F. Kelly, MC; MAJ Vincent
Mysliwiec, MC; MAJ John P. Rinard, MC; CPT Charles C. Broy, MC
Start - Completion: Funding: Periodic Review:
12/14/2005 - Sep 2008 Amarillo Pulmonary via MAMC 9/26/2006
Study Objective: This study will (1) evaluate asymptomatic nonsmokers using impulse
oscillometry (IOS) and conventional pulmonary function tests before and after bronchodilator
administration to determine the normal adult bronchodilator IOS responses to albuterol and (2)
evaluate the ability and extent to which IOS can identify airway changes in asymptomatic
smokers, patients with asthma and chronic obstructive lung disease (COPD) compared to standard
pulmonary function testing.
Technical Approach: 89 asymptomatic nonsmoker volunteers will be recruited from the hospital
staff. 89 asymptomatic smokers will be recruited from the hospital staff and family members of
patients visiting Madigan AMC for medical appointments. Based on prior literature suggesting
that 50% of asthmatics and 10-15% of COPD patients will have evidence of reversible airway
obstruction, 178 asthmatics and 890 patients with COPD will need to be enrolled to examine this
important variable. These subjects will be recruited from routine outpatient referrals to the
Pulmonary Function Lab for clinical testing.
All asymptomatic subjects will complete a questionnaire on their demographics, medical and
smoking history, and a review of systems to confirm the absence of cardiopulmonary complaints.
Height, sitting height, and weight will be measured in each subject. Four IOS measurements of 60-
90 seconds each will be performed followed by standard spirometry and lung volume
measurements. Each subject will receive 3 inhalations of albuterol 90 micrograms using a spacer
device and repeat the IOS, spirometry, and lung volume measurements after 10 minutes. Subjects
with asthma and COPD will undergo the same protocol, with the addition of completing a
validated asthma or COPD questionnaire to evaluate the severity and impact of their respiratory
disease on their daily activities.
The primary outcome variables for IOS will include the respiratory impedance (Zrs), respiratory
resistance at 5, 15, and 20 Hz (R5, R15, R20), frequency dependence from 5-15 Hz and 5-20 Hz
(R5-15, R5-20), the respiratory reactance at 5 Hz (X5) and the reactance area (AX), the resonant
frequency (frs) before and after bronchodilator administration. The primary outcome variables for
conventional pulmonary function testing will be the forced vital capacity (FVC), the forced
expiratory volume in 1 second (FEV1) and 6 seconds (FEV6), the ratio of FEV1 to FVC, body
plethysmography measurements for functional residual capacity (FRO), inspiratory capacity (IC),
and vital capacity (VC) before and after bronchodilator administration. Summary statistics,
frequency and/or contingency tables will be provided for all variables of the study. Baseline and
post-bronchodilator IOS variables will be correlated to conventional pulmonary function
measurements using a paired t test. The impact of variables age, height, sitting height, race,
gender, and allergy symptoms will be evaluated using the Analysis of Variance (ANOVA) and the
Multivariate Analysis of Variance (MANOVA). Comparison between measurements obtained in
asymptomatic nonsmokers and measurements obtained in asymptomatic smokers, asthmatics and
230
COPD subjects will be performed using ANOVA. Pearson's R correlations between IOS
measurements, conventional pulmonary function measurements, and questionnaire based
symptom scores will be obtained and the impact of the variables listed above will also be
evaluated.
Progress: This protocol remains open to patient entry, with twelve subjects enrolled in the past
eight months (Asthma (1), COPD (4), and no lung disease (7). The information obtained in this
study is from a single visit; no follow up is required unless a new diagnosis is discovered. Of the
arms in the study actively enrolling, no new diagnoses have been found. Patient recruitment
continues, but has been difficult due to frequent deployments and staff and technician shortages.
231
Detail Summary Sheets
Nutrition Care Division
232
Detail Summary Sheet
Date: 30 Sep 06 Number: 206008 Status: Ongoing
Title: Attenuation of Exertional Muscle Damage with a Nutritional Supplement
Principal Investigator: Colleen Cates-Gorang, R.D., CDE
Department: Nutrition Care Facility: MAMC
Associate Investigator(s): LTC Leslee F. Sanders, MC; Patricia A. Deuster, PhD; MAJ Steven
D. Mahlen, MS; CPT Eric Grenier, SP; CPT Michael J. Hartenstine, MS
Start - Completion: Funding: Periodic Review:
2/9/2006 - Aug 2006 DCI 9/26/2006
Study Objective: Determine the extent to which ingestion of a carbohydrate (CHO) -electrolyte
beverage with essential amino acids (EAA) to include glutamine, by soldiers during and after
strenuous exercise prevents exertional muscle damage (EMD) as compared to a carbohydrate-
electrolyte beverage alone. Biochemical analysis will include measuring plasma markers of
damage such as creatine kinase (CK) and interleukin-6 (IL-6), blood in urine and subjective
measurements of pain in a group of soldiers before, after, and 48 hours after a strenuous military
training event.
Technical Approach: The study will be a randomized, double-blind, crossover design utilizing
Fort Lewis soldiers as the study population. Subjects will be divided into two groups of a minimum
of ten per group and assigned to one of two treatment conditions, either receiving a placebo
beverage or the treatment beverage. Both beverages will be manufactured by the Gookinaid
Company per the following specifications: the placebo beverage will contain 45-60 grams of
carbohydrate per liter, 270 milligrams of sodium and 400-500 milligrams of potassium providing a
calorie range of 180-240 per liter (similar to a commonly available sports drink such as Poweraid);
the treatment beverage will consist of the placebo plus 5 grams per liter of essential amino acids
and 3.5 grams per liter of glutamine and provide 215-275 calories per liter (equivalent to adding a
glutamine powder such as ProLab Glutamine® to a sports beverage or utilizing a sports beverage
such as Growling Dog Replacement Drink®, both widely available for purchase).
The subjects will participate in a 7 V2 mile road march carrying a backpack weighted to 30% of
his/her body weight (up to a maximum of 83 pounds) - or an event similar in difficulty level. A
minimum of 1 liter of beverage will be ingested each hour during the event and an additional 1
liter of beverage consumed within two hours afterwards. After a 7-14 day washout period, the
event will be repeated, with the subjects consuming the alternate beverage; each subject is acting
as his/her own control to determine difference in treatment effect. Within subject and between
treatment group comparisons will be performed using AN OVA. Performance, metabolic and
muscle damage response data will be evaluated with repeated-measures ANOVAs and t-tests.
Dietary intake of specific nutrients will be estimated for each subject using the 4-day food record,
(previously validated and utilized at the University of Washington) and analyzed with software
from the University of Minnesota - Nutrient Data System for Research (or similar software).
Progress: Thus far, 33 Soldiers have completed both phases of study since protocol approval.
Data analyses are on-going, with aliquots currently stored for approved future laboratory analyses,
as funding allows. Statistical analyses are pending.
233
Detail Summary Sheets
Department of Nursing
234
Detail Summary Sheet
Date: 30 Sep 06 Number: 206093 Status: Ongoing
Title: Effects on Aspirated Volume, Patency, and Tracheal Mucosa using High Intermittent
Negative Pressure versus Low Continuous Negative Pressure for Subglottic Secretion Aspiration
Principal Investigator: Charlotte L. DePew, RN, MSN
Department: Nursing Facility: MAMC
Associate Investigator(s): LTC Cynthia L. Clagett, MC; MAJ Steven P. Bennett, MC; Mary S.
McCarthy, RN, PhD; Nora A. Regan, CRT; MAJ William F. Kelly, MC; MAJ Alexander S. Niven,
MC; MAJ Jeffrey B. Musser, MC
Start - Completion: Funding: Periodic Review:
8/1/2006 - Dec 2006 DCI N/A
Study Objective: Objectives: To determine the effect on aspirated secretion volume using high
intermittent versus low continuous subglottic secretion aspiration with the HiLo Evac
endotracheal tube. To determine the effect on line patency using high intermittent versus low
continuous subglottic secretion aspiration with the HiLo Evac endotracheal tube. To describe the
effect on tracheal mucosa using photographic images obtained endoscopically when evaluating
high intermittent versus low continuous subglottic secretion aspiration with the HiLo Evac
endotracheal tube.
Technical Approach: This study will use a prospective, quasi-experimental design to answer the
important questions about maintaining line patency, effectively removing secretions, and
minimizing mucosal trauma from applied negative pressure. Sixty subjects will be required with
30 per group receiving either low continuous suction or high intermittent suction. Method of
suction will alternate each month for 6 months. Patients will be included if they require
mechanical ventilation for longer than 3 days. At that point consented patients will receive a
baseline video-assisted tracheoscopy at the time of their routine subglottic suctioning intervention.
Mucosal trauma will be graded according to the Modified Mathias-Wedley Tool. From that point
on, patients will receive a once daily video-assisted tracheoscopy every one to three days with
grading of any mucosal injury. A secretion specimen taken during the tracheoscopy from above the
cuff will be submitted for microbiologic examination. Patency and secretion volume aspirated will
also be recorded daily. Data will be analyzed by Student's t test for group comparisons and
ANOVA/ANCOVA for individual / group comparisons over time. The results will be used to finalize
the evidence-based practice protocol for prevention of VAP in the MAMC ICU.
Progress: This protocol is open to patient entry, with no patients enrolled during FY06. Study
staff have asked Department of Anesthesia to add the HiLo Evac ETT to their emergency
intubation bags. Several opportunities for enrollment were missed since Anesthesia often uses
their own ETT for emergent intubation.
235
Detail Summary Sheet
Date: 30 Sep 06 Number: 203030 Status: Completed
Title: Junior Army Nurse Corps Officers' Perceptions, Experiences and Expectations of Head
Nurse Leadership
Principal Investigator: MAJ Jean M. Jones, AN
Department: Nursing Facility: MAMC
Associate Investigator(s): Lori A. Loan, RNC, Ph.D.; CPT Linda L. Blackman, AN; COL (Ret)
Eileen A. Hemman, PhD
Start - Completion: Funding: Periodic Review:
5/16/2003 - Oct 2003 DCI 1/12/2006
Study Objective: Describe Junior Army Nurse Corps Officers' perceptions, experiences, and
expectations of head nurse leadership at Madigan Army Medical Center.
Technical Approach: Selected Participants will be will be mailed information on the research
study approximately 3 weeks prior to the anticipated start date of the study through MAMC
distribution. Those volunteering to participate will be scheduled for attendance at focus group
sessions through telephone calls made by non military administrative personnel in the Nursing
Research Office 10 to 14 days prior to the session. Each focus group session will last up to 120
minutes to include administrative time for informed consent, preliminary instructions, and
answering participant questions. All focus group interviews will take place in a site in the hospital.
Locus groups will begin by the moderator introducing the agenda and sharing ground rules for
participation. Comments generated from the focus group discussions will be recorded using an
audio tape recorder and one other research team member (the PI, Cl, SC and/or RA) will be a non¬
participant observer. The facilitator will guide and focus the group discussion and interaction,
while the observer will record the discussion, note participants' interaction patterns and non¬
verbal responses as additional data. Additional field notes will be written when the facilitator and
the non-participant observer debrief after each focus group.
Progress: The final Head nurse (HN) focus group was held and data were analyzed using
Husserlian descriptive phenomenology, predominately Collazzi's approach. HN leadership
characteristics that positively impact Junior Officer (JO) retention included: (1) HNs that have a
desire to serve in the HN Role, are clinically competent and administratively effective, counsel per
standards and provide career development guidance, provided fair and equitable schedules for
civilian and military staff, use the ANC Lifecycle as a tool to guide careers (However the Lifecycle
should be based on today's optempo, include more TO&E positions and a clinical track.), mentor
JOs early, and provide recognition based on performance and achievement, not rank; and (2)
Senior leaders that mentor and develop HNs, provide realistic HN preceptorships, select HNs
based on recommendations and resumes, and only selecting the best of the best.
The study identified significant differences between HN and Junior ANC Officer
perceptions that also may negatively impact retention including: (1) Counseling-HNs perceived
that JOs wanted lengthy counseling. JOs wanted HNs to counsel quarterly and provide career
guidance; (2) Mentoring-HNs attempted to mentor JOs by giving them jobs like Schedule,
Performance or Education Coordinator to help develop leadership skills. JOs said HNs didn't know
how to properly mentor and they did not view HN delegated jobs as career enhancing; (3)
Recognition-HNs perceived that JOs want more public recognition. JOs wanted acknowledgement
based on the achievement, not rank; and (4) Scheduling-HNs perceived that JOs didn't want to
work night or weekend shifts or more than forty hours per week. JOs said their concern was the
disparity between civilian staffs empowerment to get desired schedules and military nurses' lack
of a voice when scheduling issues arose.
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Detail Summary Sheet
Date: 30 Sep 06 Number: 205117
Status: Ongoing
Title: A Qualitative Descriptive Study that Identifies Essential Competencies and Leadership
Characteristics of Army Adult Medical-Surgical Critical Care Head Nurses (dissertation)
Principal Investigator: Lori A. Loan, RNC, Ph.D.
Department: Nursing
Facility: MAMC
Associate Investigator(s): COL Roy A. Harris, AN
Start - Completion: Funding:
7/29/2005 - May 2006 DCI
Periodic Review:
7/10/2006
Study Objective: The purpose of this study is to identify and describe competencies and
leadership characteristics of Army Adult Medical- Surgical Critical Care Head Nurses. The
research questions are: (1) what are the essential competencies and leadership characteristics
identified by Army Critical Care Head Nurses themselves, (2) what are the essential competencies
and leadership characteristics of Army Critical Care Head Nurses identified by Army critical care
staff nurses, (3) what are the essential competencies and leadership characteristics of Army
Critical Care Head Nurses identified by Army Chief Nurses, and (4) what common essential
competencies and leadership characteristics of Army Critical Care Head Nurses do these three
levels of professional nursing identify?
Technical Approach: This is a qualitative, descriptive study semi- structured interviews that
include both closed-ended and open-ended questions as the primary means of data collection. Five
Army Nurse Corps nurses will be asked to participate at MAMC; the Chief Nurse, one Critical
Care Head Nurse, and three Critical Care staff nurses. Total study subjects from all sites will be
35; 5 nurses each from Walter Reed Army Medical Center, Landstuhl Regional Medical Center,
Dwight David Eisenhower Army Medical Center, Tripler Army Medical Center, Brooke Army
Medical Center, William Beaumont Army Medical Center, and Madigan Army Medical Center.
The associate investigator will conduct the interviews in all seven medical centers and at all
echelons. Documented informed consent will be obtained to allow subjects to decline enrollment.
The consent process will not be conducted by the associate investigator who will be conducting the
interviews.
Demographic data will be collected which will serve as a descriptive framework during the
analysis phase of the study. Frequencies and measures of central tendency will be utilized to
analyze the respondent's demographic data. Other analyses will be conducted using descriptive
qualitative methodology. Qualitative analysis of the data will be completed with a focus on a
comprehensive description of essential competencies and leadership characteristics of Army
Critical Care Head Nurses as perceived by the three echelons of respondents. To ensure that
ongoing analysis occurs throughout the study, the modality of constant comparative analysis will
be utilized. The data will be organized by transcribing the audiotapes of the interviews into the
Microsoft word processing program. The transcriptions will be entered into the computer program,
NVivo to facilitate the coding process. Information gleaned from this study will be de-identified
and aggregated and used as part of the associate investigator's dissertation requirement at George
Mason University. Findings will also be offered to the Army Nurse Corps, presented at nursing
conferences and published in a national nursing journal.
Progress: Data collection is completed with a total of 30 interviews from 6 different Army Medical
Centers. IRB approval at Tripler Army Medical Center took much longer than other IRBs and
therefore the timeline became too long to complete research in a timely manner for completion of
dissertation this Fall. After discussion with Dissertation Chair and committee, it was decided that
30 interviews from the remaining medical centers was sufficient to achieve saturation. All 30
237
interviews are completed and transcribed. All interviews have been sent to the interviewees for
review and comment (per proposal) and 20 have been returned. The transcripts, tapes and notes
are all secured in accordance with the proposal. There have been no complaints from any of the
interviewees either during the interview process or afterwards. Many expressed tremendous
enthusiasm in participation and were very interested in findings. This study is entering data
analysis that will utilize the NVivo 7 program. The three basic skill sets of technical, human and
conceptual (Katz) become the foci of sorting responses (per proposal). Data anlaysis will look at
responses to each question and a comparison within each echelon of leadership as well as the
contrasts between the echelons of nursing leadership. Anticipated conclusion of study is Fall 2006.
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Detail Summary Sheet
Date: 30 Sep 06 Number: 202066 Status: Ongoing
Title: Caring Interventions for Couples Who Have Miscarried
Principal Investigator: Lori A. Loan, RNC, Ph.D.
Department: Nursing Facility: MAMC
Associate Investigator(s): Kristen M. Swanson, RN, Ph.D., FAAN; Mark A Biernbaum, Ph.D.;
Kathryn Barnard, RN, Ph.D., FAAN; Martha J. Lentz, BSN, MN, Ph.D.; Margaret M.
Heitkemper, Ph.D.
Start - Completion: Funding: Periodic Review:
5/16/2002 - Oct 2004 NIH via MIPR 5/9/2006
Study Objective: The purpose of this randomized study is to compare the effects of nurse caring
(3 nurse counseling sessions), self-caring (3 home-delivered video tapes and journals), combined
caring (1 nurse counseling session plus 3 videotapes and journals) and no intervention (control) on
the emotional healing, integration of loss and couple well-being of women and their partners
(husbands or male mates) in the first year after miscarrying.
Technical Approach: 340 couples(or 680 individuals) will be recruited to participate in a 4
group, pre-test, post-test randomized study of a counseling intervention meant to reduce distress
and enhance couple well-being following miscarriage. Upon recruitment, individuals will be
informed that they may be randomized into a group that will not receive any treatment. Four
groups will be followed for 1 year. All participants will fill out 4 questionnaire packets throughout
the study period. The first will be mailed after the couple initially agrees to participate. The other
questionnaire booklets will be sent at 6 weeks, 16 weeks and 1 year after their initial enrollment
in the study.
Progress: The study reached its targeted enrollment of 340 couples during FY05. Thus far, 183
couples have completed the entire study protocol. Steady progress is being made towards
achievement of study aims. Preliminary data analyses have begun. The intervention nurses are
conducting in-home counseling sessions with couples and meet regularly for supervision. Study
data are being double entered into an SPSS secure database. Syntax files for data analysis have
been developed. Data Safety and Monitoring Board meetings occur at the University of
Washington as mandated by the funding source. Recruitment is closed at all sites: University of
Washington Medical Center, Madigan Army Medical Center, Group Health Cooperative, and
Evergreen Hospital Medical Center.
During FY06, recruitment was reported as completed and all participants completed the
interventions. Data cleaning and data analysis continues
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Detail Summary Sheet
Date: 30 Sep 06 Number: 205037 Status: Ongoing
Title: Determining the Effectiveness of a Stroke Prevention Program
Principal Investigator: Lori A. Loan, RNC, Ph.D.
Department: Nursing Facility: MAMC
Associate Investigator(s): LTC Mona 0. Bingham, AN; LTC Jon C. Allison, MC; Nancy A.
Cox, RN, BSN; Samuel C. Sorbello, RN
Start - Completion: Funding: Periodic Review:
2/3/2005 - Jan 2011 DCI 1/20/2006
Study Objective: To determine the effectiveness of an intensive one-on-one case management
program designed to control identified risk factors for stroke and reduce the incidence of stroke in
target population.
Technical Approach: This longitudinal study will use a randomized, two group repeated
measures design to compare a nurse case management stroke prevention program to standard
care provided by primary care services in order to determine the effectiveness of an intensive 1:1
case management intervention. After one year there may be a cross-over group of those control
subjects who wish to enter the case management intervention program. The study's primary
outcomes are blood pressure, LDL, HgAlc, and BMI (as calculated from measures of height and
weight). Secondary outcome measures include including incidence of vascular events,
hospitalizations, emergency room visits, progression of carotid artery disease, control of atrial
fibrillation, tobacco cessation and decreased tobacco use, and exercise level. Quality of life, mental
wellness, and overall health will also be measured through approved survey instruments available
on the MAMC web system.
Medical information from case management visits, medical records, hospital information, and
health instruments will be used to compile data for this study. Chi-square, t-tests, ANOVA with
repeated measures, and Mann- Whitney U tests will be used to compare group outcomes. The
actual 1:1 case management intervention will last one year. At the end of one year, each patient
will be re-evaluated to determine if case management services are still needed. At this time,
control patients will be asked if they would like to receive case management services until capacity
is reached for case management load. Results will be analyzed at 6 months, 1 year, and for 5 years
there after for study subjects.
Progress: This protocol remains ongoing. A11 baseline and six month data collection is complete.
One year data has been collected for over half of the participants.
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Detail Summary Sheet
Date: 30 Sep 06 Number: 204084 Status: Ongoing
Title: Impact of Inpatient Physician Order Entry on Medication Administration and Dispensing
Error Rates in the Neonatal Intensive and Intermediate Care Units
Principal Investigator: Lori A. Loan, RNC, Ph.D.
Department: Nursing Facility: MAMC
Associate Investigator(s): LTC Donna C. Whitney, MC; James A. Taylor, M.D.; Susan
Blackburn, Ph.D., RNC
Start - Completion: Funding: Periodic Review:
6/14/2004 - Jun 2005 DCI 5/20/2006
Study Objective: The proposed study will be conducted in two phases. Phase One is designed to
pilot test an observational methodology called Line Operator Safety Audit (LOSA) and modify
LOSA for use with medication error detection in the NICU/ICN and inpatient pharmacy. Phase
One will also include refinement of data collection instruments and techniques. Once the optimal
observation techniques and data collection instruments are determined, Phase Two will begin. In
this phase the number and types of observed medication administration and dispensing errors will
be compared before and after inpatient physician order entry is initiated in the NICU/ICN at
Madigan Army Medical Center.
Technical Approach: This study will examine medication errors before and after the initiation of
inpatient physician order entry (IPOE) in the Neonatal Intensive Care Unit (NICU) or
Intermediate Care Nursery (ICN), and point out what types of errors are common in this patient
population. Approximately 25 health care personnel dispensing (pharmacy personnel) or
administering (nursing personnel) medications for NICU or ICN patients will be watched until
approximately 750 opportunities-for-error have been observed. The study will use a pretest-
posttest design and appropriate statistical techniques (t-test, Mann Whitney U or chi-square) to
compare medication administration and dispensing error rates from two data collection periods- 1-
month before NICU/ICN IPOE begins and 4 months after NICU/ICN IPOE is initiated.
Information from the study will be used to develop practical error-prevention strategies.
Progress: All medication variance observations have been completed. In total, there were 253
baseline and 266 post physician order entry observations. Preliminary analysis suggests a
statistically significant decrease in the overall medication administration variance. The protocol
remains ongoing to complete data analysis already in progress.
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Detail Summary Sheet
Date: 30 Sep 06 Number: 204031
Status: Ongoing
Title: Military Nursing Outcomes Database: Analysis & Expansion (MilNOD IV)
Principal Investigator: Lori A. Loan, RNC, Ph.D.
Department: Nursing
Facility: MAMC
Associate Investigator(s): ETC Patricia A. Patrician, AN; COL Laura R. Brosch, AN
Start - Completion: Funding:
4/8/2004 - Aug 2005 Triservice Nursing Research Program via The
Geneva Foundation
Periodic Review:
12/13/2006
Study Objective: This is the fourth study (MilNOD IV) in a program of research examining nurse
staffing and patient outcomes. This particular study will shift from database development to
examining aspects of structure, process, & outcome.
Technical Approach: Data deemed valid and reliable from the study, "Establishing a Military
Nursing Outcome Database" (Brosch, 2002), will undergo secondary analyses to examine
relationships between nursing structure indicators, and patient and nurse outcome indicators. The
research team will specify a series of regression models, examining each outcome variable
separately. For survey subscales on the Nursing Work Index-Revised and the Patient Satisfaction
Survey, correlations will be performed to examine associations among independent variables and
between independent and dependent variables. Simple Pearson's correlations will indicate
whether a relationship exists between nurse and patient satisfaction.
Progress: Subjects include patients who were surveyed for the patient satisfaction indicator and
nursing personnel surveyed for their education/experience/certification activities, their job
satisfaction, and the attributes of their work environment. Retrospective data are collected from
patients participating in the pressure ulcer prevalence survey as well. Each type of survey was
conducted at MAMC once in FY'06, except the pressure ulcer prevalence data are collected
biannually. All 13 participating MTFs submitted survey data along with shift-level nurse staffing
data and patient outcome data to a project- specific electronic database during FY '06. Data
collection has now been discontinued and a data analysis plan is being formulated.
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Detail Summary Sheet
Date: 30 Sep 06 Number: 201104
Status: Ongoing
Title: Newborn Infant Speech Perception
Principal Investigator: Lori A. Loan, RNC, Ph.D.
Department: Nursing
Facility: MAMC
Associate Investigator(s): LTC Randall C. Zernzach, MC, USAF;
Christine Moon, PhD
Tricia K. Grannis, R.N.;
Start - Completion: Funding:
11/1/0168 - May 2003 UW
Periodic Review:
6/20/2006
Study Objective: Characterize the effect of experience on typically developing newborn infants'
perception of speech and language.
Technical Approach: The current proposal for research is for a 2-year study of newborn infant
discrimination of familiar and unfamiliar speech sounds. Three experiments will comprise the
study. The first will test newborns' ability to discriminate mother's voice from a stranger voice
when the speech samples are brief. The second experiment will examine whether infants respond
preferentially to their mother's native language when the samples are brief. In the third
experiment, infants will be tested for their ability to discriminate brief vowel sounds from among
well- and poorly-formed exemplars in English. Each of the three experiments will require data
from 80 participants for a total of 240 infants. Because the attrition rate for completion of the 10-
minute session is likely to be about 35%, it is expected that approximately 360 infants will be
recruited and that 120 will not complete the experiment.
Prospective participants will be 1-5 days old and will be identified from hospital records. Eligibility
will be based upon criteria that indicate typical, uncomplicated newborn development. Parents will
be contacted in their hospital rooms by the experimenters who will present the study and obtain
signed, informed consent. Infants will be transported to a quiet area near the newborn unit for a
20-minute session. A pacifier that is connected to a pressure transducer will be placed in the
infant's mouth. If the pacifier is accepted, headphones will be placed over the infant's ears. After a
1 -minute baseline period to measure sucking pressure, computer-controlled sounds at
conversational levels of intensity will be presented for 9 minutes, contingent upon infant sucking
pressure. Frequency of sucks during particular stimuli will be the dependent measure. Data
analysis will be based upon a comparison of sucking frequency during different sounds. Results of
the experiments will be presented at professional conferences and submitted as articles for
publication in professional journals.
Progress: Due to an unexpected loss of research funding, the pace of data collection slowed during
the past year; however, analysis of data in the database continued. The analyses confirm newborn
recognition and preference for mother's voice, and they extend past results by demonstrating that
pitch of the voice (fundamental frequency and/or spectral slope) is an important cue to voice
recognition by newborn infants. This is consistent with the idea that newborns are relying on
prenatal voice cues for postnatal perception. Pending replication of the pitch results, a paper on
the topic will be submitted to an infant development journal.
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Detail Summary Sheet
Date: 30 Sep 06 Number: 202075 Status: Ongoing
Title: Secondary Analysis of NICU Modified Care Environment Projects
Principal Investigator: Lori A. Loan, RNC, Ph.D.
Department: Nursing Facility: MAMC
Associate Investigator(s): Karen A. Thomas, Ph.D., RN; Susan T. Blackburn, Ph.D., RN,
LAAN; Shu-Yuann Wang, MS, RN; Ms Sara Brown, RN; Shao-Yu Tsai
Start - Completion: Funding: Periodic Review:
1/7/0168 - May 2005 DCI 5/9/2006
Study Objective: Secondary analysis of data collected in previously approved projects is
proposed. Prior human use approvals were (1) The Effects of a Modified Care Environment on the
Growth and Development of High Risk Infants, P.I. ETC Michelle T. Renaud, approved 4
September 1992, and (2) a continuation and extension, Neonatal Outcomes in a Modified NICU
Environment, P.I. ETC Michelle T. Renaud, approved 13 July 1993. Additionally these projects
were approved by the University Of Washington Human Subjects Division. Both projects included
Karen Thomas and Susan Blackburn, UW faculty, as Co-Principal Investigators.
The original projects involved comparison of two neonatal intensive care unit environments that
included reduced light and sound levels. Infants randomized to the control group remained in the
standard nursery. Both groups of infants received standard medical and nursing care in all
respects, except for the nursery environment. Data collect during the study included infant health
status, parent demographic information, duration of hospitalization, environmental sound and
light levels, neurologic and behavioral assessment and infant sleep-wake states. Infant sleep-wake
stated was measured by 3-4 hour video recordings performed at 34 weeks gestational age and
again at time of discharge. Video recordings were performed while infants were in incubators or in
open crib and display the infant's body and face.
For the second analysis, investigators are requesting permission for activities: (1) Photo copies to
be made of existing video coding sheets, (2) Access to video tapes for recording purposes, (3) Use of
existing data base by the three graduates named above.
Technical Approach: The proposed research is a secondary analysis of data from a previously
approved project that was conducted at MAMC in conjunction with nurse researchers from the
University of Washington Department of Family and Child Nursing. Permission is requested for
use of data by a total of three nursing graduate students. Computer files containing the data from
the original project, excluding identifiers, is currently in the possession of Karen Thomas.
Permission is requested to photocopy the video coding sheets, currently held at MAMC for use by
investigators at the University of Washington. Permission is also requested for temporary use of
the videotapes at the U.W. The video coding sheets will be used to enter the raw data into a
computer file. Videos will be used to determine reliability of original coding and to code additional
infant behaviors and care giving activities.
Progress: One doctoral student, Shu-Yuann Wang, continues to analyze data from the parent
project. This data is anonymized; investigators at the University of Washington do not have access
to the original code list, and the data set does not include any information which would allow
identification of subjects. Ms. Wang will complete her dissertation by June 2006. Two graduates,
Shao-Yu Tsai and Sara Brown, whose Masters theses were based on the secondary analysis, along
with Dr. Karen Thomas, have submitted a journal manuscript based on study findings. Ms. Tsai's
poster presentation at the Western Institute for Nursing conference (An Exploratory Analysis:
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Environmental Modifications on the Sleep-Wake State in Preterm Infants - Portland, OR, 2004)
received an award for doctoral student research.
245
Detail Summary Sheet
Date: 30 Sep 06 Number: 206108 Status: Ongoing
Title: Army Nurse Corps Officers' Deployment Experiences and Reintegration
Principal Investigator: COL Laurie A. McNabb, AN
Department: Nursing Facility: MAMC
Associate Investigator(s): Lori A. Loan, RNC, Ph.D.; LTC Denise Hopkins-Chadwick, AN;
Mary S. McCarthy, RN, PhD
Start - Completion: Funding: Periodic Review:
7/10/2006 - Jun 2007 DCI N/A
Study Objective: To explore the many factors that impact nurses' ability to perform their jobs
during all phases of a deployment; prior to the deployment, during the deployment, and during the
post-deployment phase. Outcomes of this study will serve as the basis for the development of the
best strategies to support nurses prior to and following a deployment in order to facilitate the
smoothest transition, between workplaces.
Technical Approach: Prospective Data Collection Procedures: Army Nurse Corps Officers will be
recruited based on the inclusion criteria and availability. Nurses interested in participating in the
study will be contacted by phone or email. During this initial call, one of the study investigators
will discuss a variety of issues with each participant such as the study purpose, what will be
needed from them as participants, who will be at the group or interview, and other specifics of the
focus group sessions. They will be given information about the study and their questions will be
answered. Those volunteering to participate will be scheduled for attendance at focus group
sessions or interviews through telephone calls or personal interactions carried out 7 to 14 days
prior to the session. To increase attendance, participants will again be contacted telephonically by
a research team member 24 hours prior to the date and time of the session (Goldstein &
McDonald, 1987; Krueger, 1988; Stewart & Shamdasani, 1990). Participants will also be given a
demographic data collection sheet and asked to complete it and bring it to the focus group meeting.
These sheets will be collected from participants after consenting is complete. If participants fail to
bring the sheet, they will be asked to supply demographic information at the time of the focus
group session.
Progress: This protocol remains open to enrollment. Twelve subjects have participated in focus
groups at MAMC so far.
246
Detail Summary Sheet
Date: 30 Sep 06 Number: 206107 Status: Ongoing
Title: Menstruation During Deployment: Women's Attitudes Towards Menstrual Suppression
Principal Investigator: LTC Lori L. Trego, AN
Department: Nursing Facility: MAMC
Associate Investigator(s): Lori A. Loan, RNC, Ph.D.; LTC Denise Hopkins-Chadwick, AN; 1LT
Sandra L. Gordy, AN
Start - Completion: Funding: Periodic Review:
7/10/2006 - Aug 2007 DCI N/A
Study Objective: Objective is to perform instrument development and testing of a military-
specific measure of the experience of menstruation and associated attitudes towards menstrual
suppression in a deployed environment. Specific Aims are to (1) establish the reliability (internal
consistency) of an instrument that measures military women's experiences of menstruation and
attitudes towards menstrual suppression and (2) establish the validity (content, face, construct,
convergent, discriminant) of an instrument that measures military women's experiences of
menstruation and attitudes towards menstrual suppression.
Technical Approach: Data collection will be the administration of a paper and pencil survey
consisting of the Military Women's Attitudes Towards Menstrual Suppression, the Attitudes
Towards Menstrual Suppression Scale (ATMS), the Menstrual Attitudes Questionnaire (MAQ),
and a Deployed Menstrual Health Practice Questionnaire (DMHPQ). Targeted sample size per
power analysis is 300-500 participants, as required for factor analysis. Psychometric testing with
this sample size allows for tests of internal consistency and item evaluation in the assessment of
reliability as well as exploratory factor analysis for construct validation. Several methods of
construct validity have been chosen for this study: content validity, face validity, construct
validity, and convergent and discriminant construct validity. The sample will therefore complete a
questionnaire that consists of the MW ATMS, as well as two other valid instruments that will be
used to test convergent and discriminant validity: the Menstrual Attitude Questionnaire (MAQ)
and the Attitudes Towards Menstrual Suppression scale (ATMS).
Progress: Twenty-three Soldiers have participated in this study. There have been no adverse
occurrences and no preliminary findings are available. Enrollment will continue during FY07.
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Detail Summary Sheet
Date: 30 Sep 06 Number: 206002 Status: Completed
Title: Military Women's Thoughts about Menstruation and Menstrual Suppression During
Deployment
Principal Investigator: LTC Lori L. Trego, AN
Department: Nursing Facility: MAMC
Associate Investigator(s): Lori A. Loan, RNC, Ph.D.
Start - Completion: Funding: Periodic Review:
10/14/2005 - Oct 2006 DCI N/A
Study Objective: This study will be conducted in two phases. The purpose of Phase 1 is to
describe menstrual experiences of women who have been deployed to a military theater of
operations and to explore their experiences with menstrual suppression. Phase 1 research
questions are: (1) How do military women manage menses while deployed? (2) How do military
women feel about using continuous oral contraceptives for suppression of menses while they are
deployed?
The purpose of Phase 2, pilot instrument development and testing, is to generate an instrument
that measures military women's attitudes towards menstruation and menstrual suppression.
Phase 2 research questions are: (1) What are the initial psychometric properties of the instrument?
(2) To what extent is further use of the instrument feasible?
Technical Approach: Phase 1, Interviews: A qualitative descriptive approach will be utilized to
explore attitudes towards menstruation and menstrual suppression among military women who
have returned from a deployment to a theater of military operations. The projected sample size is
30 women, or until themes become repetitive. Data Collection: Sampling will occur at the Fort
Lewis SRP site. Subjects will participate in a focused interview utilizing open-ended questions
which have been derived from a review of literature. Questions will be focused on the experiences
of menstruation and suppression of menstruation using continuous oral contraceptives while in a
deployed environment. The interviews will be limited to 30 minutes, being cognizant of the time
constraints on these women's live. The interviews will be conducted in a private area within the
SRP site. The data will be audio tape recorded and transcribed verbatim by either a qualified
transcriptionist or the PI. Data Analysis: Inductive content analysis will be conducted to
determine themes which describe the menstrual experiences and suppression of menses, as it is
applicable, of deployed women.
Phase 2, Instrument development: The Phase 1 themes will be utilized in the construction of a
military-specific tool to measure military women's menstrual attitudes and their attitudes towards
menstrual suppression during deployment. Items for the measure will be generated based on
themes from the interviews. A women's health expert panel, will be consulted during item
generation. Content validity will be determined by both the women's health expert panel and a lay
panel, which will consist of military women. Revisions to the instrument will be made based on
content validity assessments. The expert panel will again be consulted. The final step of
instrument development is a pilot test of the instrument on 50-60 women. The sample will be from
the SRP site. Recruitment will occur in the same manner as with the interviews. The instrument
will be administered in a private area of the SRP. A face validity assessment will be included with
the instrument for the pilot subjects to complete. The pilot data will be analyzed for reliability and
feasibility. Based on the results of the pilot data, the instrument will be revised and ready for
future study. The future study would determine the instrument's validity and reliability.
248
Progress: Phase 2, "Instrument Development," has been conducted. Based on the results of
Phase 1, the instrument, "Military Women's Attitudes Towards Menstrual Suppression" was
revised and pilot tested according to protocol procedures. Data analysis was performed according
to protocol and the instrument was found to have sufficient reliability and validity for future
study. Refer to protocol #206107 for next study in the development of this instrument. This
protocol was reported as completed during FY 2006.
249
Detail Summary Sheets
Anesthesia Students, Department of Nursing
250
Detail Summary Sheet
Date: 30 Sep 06 Number: 204112 Status: Completed
Title: Efficacy of Preoperative Valerian (Night Before) on Day of Surgery Anxiety
Principal Investigator: CPT Mary K. Hannon, AN
Department: Nursing/ Anesthesia Facility: MAMC
Associate Investigator(s): CPT Angela M. Downs, AN; Mark D. Hachey, CRNA
Start - Completion: Funding: Periodic Review:
11/5/2004 - Oct 2005 DCI 8/23/2005
Study Objective: To determine if valerian reduces anxiety in patients undergoing general or
regional anesthesia when administered the night before surgery.
Technical Approach: Recruitment: Identification of potential candidates for participation in the
study will be accomplished by prescreening of the surgical roster, and identified candidates
recruited during the pre-anesthesia interview. CPT Angela Downs or CPT Mary Kate Hannon will
complete consent after the pre-anesthesia interview. Informed consent will be obtained prior to the
administration of any of the anxiety measuring instruments (VAS/SAI). Upon collection of
demographic data, a standardized direction and information statement will be read to each
participant. Once the participant verbalizes understanding of the process, the SAI and VAS in
relation to anxiety of the upcoming surgery will be administered. The principle or associate
investigators will be present in the room for this process to answer any questions, and to collect
and secure the data. Randomization of test subjects will be accomplished by pre-prepared chart
calculated by Mr. Troy Patience of the Department of Clinical Investigations, MAMC using
Microsoft Excel. Patients will receive either placebo, or 800mg active valerian according to the
randomization chart. Each day investigators will sign out approximately 15 doses of the pre¬
numbered standard plastic prescription vials containing the valerian or placebo. Distribution will
be accomplished by the investigators during the preoperative interview. An instruction sheet
explaining possible side effects of this medication will be provided to the subjects, as well as
instructions if a suspected allergic reaction or acute side effects occur. The time frame of actual
administration will be approximately 2200 hrs the night before surgery, or at the hour of sleep, in
accordance with other surgical restrictions, i.e., NPO after midnight.
Re-evaluation of test subjects: Participants will be asked to repeat both the VAS and SAI forms
while in the preoperative holding area and prior to the insertion of IV catheter(s) or any other
surgical adjunct. Either investigator will again collect the VAS and SAI form data assuring
consistency and confidentiality. Outcome variables are the level of anxiety that will be measured
using the STAI-S questionnaire and VAS, with an anticipated reduction in the level of anxiety in
individuals taking the 800mg valerian versus the placebo. Differences between groups will be
determined by a statistical analysis of the SAI and the VAS scores separately using Analysis of
Covariance.
Progress: This protocol was reported as completed in October 2005, with 143 subjects enrolled.
Findings: Under the conditions of this study, there were no significant differences between the pre
and post SAI and VAS for either the placebo or valerian group. Serendipitously, the investigators
found a significant difference in preoperative anxiety between males and females. Postulated
reasons there was no significant difference (1) valerian has no efficacy, (2) timing of dose
administration and post test, (3) dose of valerian administered, (4) single dose versus multiple
doses, and (5) influence of gender roles on anxiety.
251
Detail Summary Sheets
Department of Obstetrics/Gynecology
252
Detail Summary Sheet
Date: 30 Sep 06 Number: 206042 Status: Completed
Title: Resident Training in Assessment of the Sexual Assault Patient Utilizing Simulation
Principal Investigator: CPT Anne C. Burris, MC
Department: OB/GYN Facility: MAMC
Associate Investigator(s): MAJ Shad H. Deering, MC; LTC Michael K. Chinn, MC
Start - Completion: Funding: Periodic Review:
1/6/2006 - Jan 2006 DCI N/A
Study Objective: The objective is to evaluate the use of a simulation-based training program on
resident comfort with and understanding of evaluation of a sexually assaulted patient.
Technical Approach: This study plans to utilize the NOELLE childbirth simulator module at the
Anderson Simulation Center to both evaluate resident performance of the evaluation of a sexual
assault patient as well as investigate their comfort level with the procedure. This evaluation is to
be done before and after simulation testing to see if this is a helpful model that should be
incorporated into our standard simulation curriculum.
Progress: Results: After training, residents reported that they had a better understanding of the
procedure for the examination, what medications should be given for STD prophylaxis, what
anatomic findings must be recorded, and the chain of custody that must be maintained.
Conclusions: A simulation-based course can improve resident confidence with the performance of
the examination of a sexual assault patient. This training is especially important in the
explanation of the requirements for the collection of evidence.
253
Detail Summary Sheet
Date: 30 Sep 06 Number: 205140 Status: Ongoing
Title: Continuous Use of the Oral Contraceptive for Menstrual Cycle Suppression and the
Effects on Bone Density; a Prospective, Randomized, Clinical Trial
Principal Investigator: ETC Michael K. Chinn, MC
Department: OB/GYN Facility: MAMC
Associate Investigator(s): Leslie Miller, M.D.; LTC Antonio G. Balingit, MC; Nancy A.
Poffenberger, PAC, Ph; COL Diane M. Flynn, MC; LTC Wendy Ma, MC; LTC Jeffery L. Clemons,
MC; COL Jon A. Proctor, MC; Gregory E. Chow, MD; CPT Tammy J. Mantzouris, MC; CPT
Andrew E. Fong, MC
Start - Completion: Funding: Periodic Review:
1/13/2006 - Dec 2011 DCI 10/19/2006
Study Objective: To identify the dose of ethinyl estradiol (EE) in combination with levonorgestrel
(LNG) or norethindrone acetate (NETA) that, when taken daily, results in rapid and sustained
amenorrhea over two years with minimal changes in bone density.
Technical Approach: This study looks at what pill dose, when taken every day, will work the
fastest to stop all period bleeding and which dose will keep the bleeding away for two years of daily
use. Women will provide a monthly report of pill use and bleeding and have their bone density
measured at baseline and after two years to see if the two estrogen doses or two progestin types
will vary these and other safety effects. In addition, women stopping the study drug will be
followed until menstruation returns to document reversibility. Female soldiers need to know which
dose of birth control pill can induce menstrual cycle suppression, the safety of taking these pills
every day for up to 2 years, the effects of an induced amenorrhea on their bone density, and the
time it takes for menses to return following suppression.
Progress: Initiation of this protocol is pending funding. An amendment was submitted due to an
offer of fewer funds than requested. The study has changed from a four arm to a two arm trial
looking at the lower estrogen doses. Enrollment was dropped from 720 to 360, and length of
subject involvement shortened from 24 to 18 months. The study also would no longer be providing
menstrual hygiene products to subjects or be able to hire a study provider (ARNP); just a dedicated
research coordinator.
254
Detail Summary Sheet
Date: 30 Sep 06 Number: 81035 Status: Ongoing
Title: GOG 0041: Surgical Staging of Ovarian Carcinoma
Principal Investigator: LTC Louis A. Dainty, MC
Department: OB/GYN Facility: MAMC
Associate Investigator(s): LTC Jane Shen-Gunther, MC
Start - Completion: Funding: Periodic Review:
1/16/1981 - Indef GOG 9/21/2006
Study Objective: To determine the spread of ovarian carcinoma to intraperitoneal structures and
retroperitoneal lymph nodes by direct examination, cytologic sampling, and biopsy; to establish a
surgical protocol for patients entered into GOG ovarian cancer treatments protocols; to determine
the complication rate of the procedures.
Technical Approach: This protocol is being performed as a statistical protocol on patients who
have surgery as standard treatment. Eligible patients will be those who have Stages I, II, or III
ovarian carcinoma. Patients undergoing total abdominal hysterectomy, bilateral or unilateral
salpingo-oophorectomy, bivalving of the ovary, selective pelvic and para-aortic lymphadenectomy,
omental biopsy, or peritoneal cytology sampling will be studied. They will not be given any
preoperative treatment, but will be subjected to a complete and thorough evaluation before
surgery. All patients will be explored and the steps for surgery will be as standard surgery
dictates. Specific observations will be made as to the findings. If fluid is not present, washings will
be taken from the inside of the abdomen to study cells. A thorough examination of all structures
from the diaphragm to the pelvic floor will be carried out. After surgical staging, patients will be
transferred to the appropriate treatment protocol or to standard treatment if no protocol is
available.
Progress: This protocol closed to patient entry in February 1987, with thirteen patients enrolled.
Three patients remain disease free and continued to be followed at MAMC during FY06. Final
analysis of this trial appears in the January 1988 GOG Statistical Report. The manuscript derived
from this trial was published in Surg. Gynecol. Obstet 1989.
255
Detail Summary Sheet
Date: 30 Sep 06 Number: 81105 Status: Ongoing
Title: GOG 0052: A Phase III Randomized Study of Cyclophosphamide Plus Adriamycin Plus
Platinol Versus Cyclophosphamide Plus Platinol in Patients with Optimal Stage II Ovarian
Adenocarcinoma
Principal Investigator: LTC Louis A. Dainty, MC
Department: OB/GYN
Facility: MAMC
Associate Investigator(s): LTC Jane Shen-Gunther, MC
Start - Completion: Funding:
8/21/1981 - Indef GOG
Periodic Review:
9/21/2006
Study Objective: To determine, in optimal Stage III ovarian adenocarcinoma, if the addition of
adriamycin to cyclophosphamide plus cis-platinum improves progression-free interval, frequency of
negative second-look laparotomy and survival. This protocol replaces GOG 0025.
Technical Approach: Eligible patients are those more than six weeks post-operative with proven
primary Stage III ovarian adenocarcinoma confined to the abdominal cavity and its peritoneal
surfaces with residual tumor masses after surgery no larger than 1 cm in diameter. Patients with
prior chemo or radiotherapy are ineligible. Patients will be randomized to cyclophosphamide plus
Platinol every three weeks for eight courses or to cyclophosphamide and Platinol plus adriamycin
every three weeks for eight courses. After eight courses those with less than clinically complete
response will go off study and be followed for survival; those with clinically complete response will
have second-look surgery to validate the complete response or to remove residual tumor masses.
Patients will then be followed for approximately five years for survival rates.
Progress: This protocol closed to patient entry in July 1985, with six patients enrolled. One
patient remains disease free and continued to be followed at MAMC during FY06. Final analysis of
the study appears in the July 1988 GOG statistical report. Seven abstracts and publications (listed
in the GOG statistical report) evolved from this clinical trial.
256
Detail Summary Sheet
Date: 30 Sep 06 Number: 84033 Status: Ongoing
Title: GOG 0072: Ovarian Tumors of Low Malignant Potential: A Study of the Natural History
and a Phase II Trial of Melphalan and Secondary Treatment with Cisplatin in Patients with
Progressive Disease
Principal Investigator: LTC Louis A. Dainty, MC
Department: OB/GYN
Facility: MAMC
Associate Investigator(s): LTC Jane Shen-Gunther, MC
Start - Completion: Funding:
2/17/1984 - Indef GOG
Periodic Review:
9/21/2006
Study Objective: To evaluate the biologic behavior of ovarian tumors of low malignant potential;
to evaluate the effectiveness of chemotherapy against this disease (initially, a Phase II study of
melphalan); and to evaluate the response rate to cisplatin in melphalan failures.
Technical Approach: Patients without prior chemotherapy of radiotherapy who have had
adequate surgical staging will be eligible. Patients with no grossly visible residual disease will
receive no treatment and be followed for five years if there is no subsequent disease. If there is no
grossly visible clinically apparent residual for 12 months, the patients will have second look
surgery and then proceed to melphalan treatment (5 days every four weeks) or follow-up (complete
response). With progression after melphalan, patients will proceed to third look and cisplatin
treatment (once every three weeks for eight weeks) or follow-up. If there is no evidence of response
after three courses of cisplatin, the treatment will be discontinued. Patients who have progression
during the first 12 months will be treated as above except they will proceed directly to melphalan
treatment without second look surgery. Follow-up will be for a minimum of five years with clinical
examination every three months for the first two years, then every six months thereafter.
Progress: This protocol closed to patient entry in February 1992, with ten patients enrolled. Five
patients continued to be followed at MAMC during FY06, three patients have been lost to follow¬
up and two patients with no evidence of disease continue to be followed out-of-state. Statistical
analysis appears in the July 2002 GOG Statistical Report. Manuscript derived from this trial was
published in JCO 1995.
257
Detail Summary Sheet
Date: 30 Sep 06 Number: 84074 Status: Ongoing
Title: GOG 0078: Evaluation of Adjuvant VP-16, Bleomycin, and Cisplatin (BEP) Therapy in
Totally Resected Choriocarcinoma, Endodermal Sinus Tumor, Embryonal Carcinoma and Grade
3 Immature Teratoma of the Ovary, Pure and Mixed with Other Elements
Principal Investigator: LTC Louis A. Dainty, MC
Department: OB/GYN
Facility: MAMC
Associate Investigator(s): LTC Jane Shen-Gunther, MC
Start - Completion: Funding:
8/17/1984 - Indef GOG
Periodic Review:
9/21/2006
Study Objective: To evaluate the effect of adjuvant vinblastine, bleomycin, and cisplatin (VBP)
chemotherapy in patients with endodermal sinus tumor and choriocarcinoma of the ovary (pure
and mixed) after removal of all gross tumor; to evaluate the role of serum markers, especially
alpha fetoprotein and HCG, in predicting recurrence; to evaluate the role of reassessment
laparotomy in determining response, detecting early relapse, and planning further therapy; and to
compare the biologic behavior of pure endodermal sinus tumors with mixed germ cell tumors
containing endodermal sinus elements. Per addendum of Jan. 87: to evaluate the acute and
chronic toxicity of this chemotherapy on gonadal and reproductive function.
Technical Approach: Patients with totally resected Stage I choriocarcinoma, endodermal sinus
tumor, or embryonal carcinoma of the ovary with negative peritoneal washings, normal (or falling
at a rate that does not suggest residual disease) serum AFP and beta-HCG levels, and adequate
bone marrow, renal, and hepatic function will be studied. Stages II and III will also be eligible if
all gross tumor is resected. After recovery from surgery, patients will receive 3 cycles of VBP
therapy. Patients who show evidence of progression while on VBP therapy will be candidates for
GOG Protocol 26. Patients completing three cycles of treatment clinically free of disease will
undergo reassessment laparotomy. Patients with recurrent disease at reassessment laparotomy
will be candidates for GOG Protocol 26. To be eligible a patient will receive at least one week of
chemotherapy and live another two weeks. Each patient will remain on study until adverse effects
prohibit further therapy or until evidence of progression is noted. Per addendum of Jan. 86: the
title has been changed as shown above; vinblastine has been replaced by VP- 16; Grade 3 immature
teratoma has been added for entry and evaluation.
Progress: This protocol closed to patient entry in February 1992, with one patient enrolled who
remains disease-free with a last follow-up (out-of-state) in FY02. Final analysis of this study
appears in the July 1993 GOG Statistical Report. Manuscripts derived from this clinical trial had
been published in 1994.
258
Detail Summary Sheet
Date: 30 Sep 06 Number: 86089 Status: Ongoing
Title: GOG 0085: A Randomized Comparison of Hydroxyurea versus 5-FU Infusion and Bolus
Cisplatin as an Adjuvant to Radiation Therapy in Patients with Stages II-B, III, and IV-A
Carcinoma of the Cervix and Negative Para-Aortic Nodes
Principal Investigator: LTC Louis A. Dainty, MC
Department: OB/GYN
Facility: MAMC
Associate Investigator(s): LTC Jane Shen-Gunther, MC
Start - Completion: Funding:
9/19/1986 - Indef GOG
Periodic Review:
9/21/2006
Study Objective: To determine whether hydroxyurea or the combination of 5-FU and cisplatin is
superior as a potentiator of radiation therapy in advanced cervical carcinoma and to determine the
relative toxicities of hydroxyurea versus the combination of 5-FU and cisplatin when given
concurrently with radiation therapy.
Technical Approach: Patients with invasive squamous cell, adenocarcinoma, or adenosquamous
carcinoma of the cervix, Stages II-B, III, and IV-A, who meet the eligibility requirements as listed
in the protocol, will undergo clinical staging as permitted by FIGO rules. All patients will undergo
surgical staging to include extraperitoneal sampling of the para-aortic lymph nodes, peritoneal
cytology, and intraperitoneal exploration. Patients with cancer confined to the pelvis will receive
pelvic irradiation and will be randomly assigned to receive either concomitant 5-FU and cisplatin
or hydroxyurea. Patients with disease outside the pelvis are not eligible for this protocol. The
study will continue as long as treatment protocols remain activated. The patients will be followed
for two years and then every six months for three additional years.
Progress: This protocol closed to patient entry in December 1990, with two patients were
enrolled. One patient was lost to follow-up (last seen at MAMC in 1985). The second patient has
been disease free and continued to be followed at MAMC during FY06. Final statistical analysis
appears in the July 1997 GOG Statistical Report. Two abstracts and a publication (listed in the
GOG statistical report) have been derived from this clinical trial.
259
Detail Summary Sheet
Date: 30 Sep 06 Number: 87104 Status: Ongoing
Title: GOG 0092: Treatment of Selected Patients with Stage IB Carcinoma of the Cervix After
Radical Hysterectomy and Pelvic Lymphadenectomy: Pelvic Radiation Therapy versus No
Further Therapy
Principal Investigator: LTC Louis A. Dainty, MC
Department: OB/GYN
Facility: MAMC
Associate Investigator(s): LTC Jane Shen-Gunther, MC
Start - Completion: Funding:
8/21/1987 - Indef GOG
Periodic Review:
9/21/2006
Study Objective: To determine the value of adjunctive pelvic radiation in the treatment of Stage
IB carcinoma of the cervix but with selected high-risk factors; to determine the recurrence-free
interval, survival and patterns of failure in those patients; and to determine the morbidity of
adjunctive pelvic radiation following radical hysterectomy.
Technical Approach: All patients with Stage IB cancer of the cervix who have been treated by
radical hysterectomy and pelvic node dissection and found to have cancer confined to the cervix
and who have a large tumor and/or lymph or blood vessel invasion in the cervix will be eligible to
enter the study. Patients will be randomized to one of two groups. One group will receive external
radiation therapy to the pelvis and the other group will receive no further therapy. Patients
assigned to receive the radiation therapy will receive the therapy daily for 4 to 6 weeks. Both
groups of patients will be required to have check-ups every three months for three years and then
every six months for two more years.
Progress: This protocol closed to patient entry in December 1995, with one patient enrolled in FY
1988, who remains disease free and continued to be followed at MAMC during FY06. Final
analysis appears in the January 1999 GOG Statistical Report. An abstract and publication have
been derived from this clinical trial.
260
Detail Summary Sheet
Date: 30 Sep 06 Number: 87028 Status: Ongoing
Title: GOG 0095: Randomized Clinical Trial for the Treatment of Women with Selected Stage IC
and II (A,B,C) and Selected IAi and IBi and IAii and IBii Ovarian Cancer, Phase III
Principal Investigator: LTC Louis A. Dainty, MC
Department: OB/GYN Facility: MAMC
Associate Investigator(s): LTC Jane Shen-Gunther, MC
Start - Completion: Funding: Periodic Review:
11/21/1986 - Indef GOG 9/21/2006
Study Objective: In definitively staged patients who have tumor involving one or both ovaries
with pelvic extension and/or malignant ascites and/or positive peritoneal washings and in those
Stage IAi and IBi patients with poorly differentiated tumors and stage IAii and IBii (all grades) to:
compare the progression-free interval and overall survival of the two treatment regimens;
determine the patterns of relapse for each form of therapy; and define the relative toxicities of the
two treatment approaches.
Technical Approach: The study design will be a randomized comparison between the standard
adjuvant treatment (P32) and an experimental arm of short term intensive adjuvant combination
chemotherapy with cyclophosphamide/cisplatin in patients with ovarian cancer. One to two weeks
following surgery, P32 therapy will be started. Fifteen millicuries of chromic phosphate suspension
mixed in 500 cc of normal saline will be infused into the peritoneal cavity via the peritoneal
dialysis catheter after a technetium scan or abdominal x-rays with contrast material has
demonstrated adequate distribution. In order to facilitate distribution of the P32, the patient will
be turned every 15 minutes to the left side, onto the back, in Trendelenburg and reverse
Trendelenburg positions, onto the right side and so on for two hours following the infusion.
Chemotherapy will consist of cyclophosphamide, 1 mg/m2 I.V., on day 1 plus cisplatin, 100 mg/m
IV, on day 1 administered one hour after cyclophosphamide. Cycles of combination chemotherapy
will be repeated every three weeks depending upon the time to recovery of the blood counts to
pretreatment level. Cycles of chemotherapy will be repeated for a total of three cycles. Patient
follow-up will continue until death, loss of follow-up, or termination of the study. Patients will
remain on study until disease progression or adverse effects dictate otherwise. An adequate trial is
defined as receipt of at least one course of therapy and one follow-up visit.
Progress: This protocol closed to patient entry in March 1994, with five patients enrolled. One
patient remains disease free and continued to be followed at MAMC during FY06. Final analysis of
this trial appears in the July 2000 GOG Statistical Report. Abstracts and manuscripts derived
from this trial have been published as listed in the GOG Statistical Report.
261
Detail Summary Sheet
Date: 30 Sep 06 Number: 87091
Status: Ongoing
Title: GOG 0099: A Phase III Randomized Study of Adjunctive Radiation Therapy in
Intermediate Risk Endometrial Adenocarcinoma
Principal Investigator: ETC Louis A. Dainty, MC
Department: OB/GYN
Facility: MAMC
Associate Investigator(s): ETC Jane Shen-Gunther, MC
Start - Completion: Funding:
7/17/1987 - Indef GOG
Periodic Review:
9/21/2006
Study Objective: To determine if patients with intermediate risk endometrial adenocarcinoma
who have no spread of disease to the lymph nodes benefit from postoperative pelvic radiotherapy
and to evaluate how the addition of pelvic radiotherapy will alter the site and rate of cancer
recurrence in these intermediate risk patients.
Technical Approach: Patients with primary histologically confirmed Grade 2 or 3 endometrial
adenocarcinoma (endometrioid, villoglandular, mucinous and adenosquamous) and clear cell
carcinoma will be eligible. Patients must have had a total abdominal hysterectomy, bilateral
salpingo-oophorectomy, selective pelvic and para-aortic node sampling, pelvic washings and found
to be surgical Stage 1 with myometrial invasion. Following surgery, patients will be randomized to
no additional treatment of pelvic radiation therapy to begin no later than eight weeks after
surgery. Those randomized to radiation therapy will be treated with AP and PA parallel ports with
each port being treated each day. A daily tumor dose of 180 cGy will be given to a total dose of
5040 cGY in approximately six weeks. Each patient will be followed with regular visits occurring
every three months for the first two years, every six months for the third, fourth and fifth years,
and yearly thereafter.
Progress: This protocol closed to patient entry in July 1995, with three patients enrolled. All are
clinically disease free and continued to be followed during FY06. Final analysis appears in the
January 1999 GOG Statistical Report. Two abstracts were published. Manuscript derived from
this clinical trial is under revision for publication.
262
Detail Summary Sheet
Date: 30 Sep 06 Number: 93063 Status: Ongoing
Title: GOG 0123: A Randomized Comparison of Radiation Therapy & Adjuvant Hysterectomy vs
Radiation Therapy & Weekly Cisplatin & Adjuvant Hysterectomy in Patients with Bulky Stage
IB Carcinoma of the Cervix
Principal Investigator: LTC Louis A. Dainty, MC
Department: OB/GYN
Facility: MAMC
Associate Investigator(s): LTC Jane Shen-Gunther, MC
Start - Completion: Funding:
5/6/1994 - Indef GOG
Periodic Review:
9/21/2006
Study Objective: To evaluate the addition of weekly chemotherapy with Cisplatin during
radiation therapy in patients with bulky Stage IB carcinoma of the cervix.
Technical Approach: This study randomizes patients to two different treatment regimens. Both
regimens include radiation therapy followed by hysterectomy. Regimen I - Radiation Therapy Plus
Adjuvant Hysterectomy - Patients will undergo combined external and intracavitary radiation
therapy followed by extrafascial hysterectomy (total doses of 13000 cGy). Regimen II - Radiation
Therapy Plus Weekly Cisplatin Infusion Plus Extrafascial Hysterectomy. Patient will undergo
radiation therapy to receive a total dose of 13000 cGy using a combination of external and
intracavitary radiation therapy. Each week during external radiation therapy and during the
intracavitary applications the patient will receive an infusion of cisplatin 40 mg/m2 not to exceed
70 mg maximum in any single infusion, up to a maximum of 6 doses of cisplatin. Extrafascial
hysterectomy will be carried out no later than six weeks following the last day of treatment in both
regimens.
The principal parameters to determine the efficacy of weekly cisplatin during radiotherapy
are: 1) Outcome variables (recurrence-free interval (RF), survival and local control rate); 2) Tumor
characteristics; 3) Host characteristics; 4) Adverse effects; 5) Therapy administered.
Progress: This protocol closed to patient entry in April 1997, with one patient enrolled who
remains disease free and continued to be followed during FY06.
263
Detail Summary Sheet
Date: 30 Sep 06 Number: 206029 Status: Ongoing
Title: Simulation Training for Postpartum Hemorrhage
Principal Investigator: MAJ Shad H. Deering, MC
Department: OB/GYN Facility: MAMC
Associate Investigator(s): None.
Start - Completion: Funding: Periodic Review:
12/14/2005 - Jan 2006 DCI N/A
Study Objective: To have OB/GYN residents perform a simulated postpartum hemorrhage
scenario to evaluate their clinical management skills and evaluate a standardized grading form.
Technical Approach: A standard postpartum hemorrhage simulation has been designed using
the NOELLE mannequin and the new uterine hemorrhage model at the Anderson Simulation
Center (designated for use by OB/GYN). Standardized objective and subjective evaluation sheets
have been created to evaluate resident's performance. Prior to beginning the simulation, residents
will be given a case scenario describing the patient's clinical situation. Residents will enter the
room and address the active bleeding that is occurring. All simulations will be digitally recorded
with at least two evaluators present to assess the resident's performance using the standard
evaluation forms. Residents will be able to perform an examination and ask for medications to be
administered. An empty syringe will be used by a staff member playing the part of the nurse to
"administer" any medications requested and the resident will be made to clarify the dose and route
of the medication. The simulation will end when the resident has performed an appropriate
physical examination, fundal massage, and administered two medications in the correct dose and
route, or when a total of 5 minutes has expired. After the simulation, the resident will be shown
their grading scores and additional instruction will be performed in any areas that were deficient.
Progress: This protocol remains ongoing with fourteen residents from MAMC who took part in
this study during FY06. All fourteen completed the simulation training protocol and data analysis
is currently being conducted.
264
Detail Summary Sheet
Date: 30 Sep 06 Number: 206098
Status: Ongoing
Title: Serum Estradiol Levels in Patients with Polycystic Ovarian Syndrome undergoing
Ovulation Induction with Clomiphene Citrate
Principal Investigator: CPT Shannon K. Flood, MC
Department: OB/GYN
Facility: MAMC
Associate Investigator(s): COL Jon A. Proctor, MC
Start - Completion: Funding:
6/5/2006 - May 2007 DCI
Periodic Review:
N/A
Study Objective: To correlate serum estradiol levels and ovulation rates in patients with
polycystic ovarian syndrome undergoing ovulation induction with clomiphene citrate.
Technical Approach: This is a prospective observational study to analyze the relationship
between serum estradiol levels and ovulation rates in women with polycystic ovarian syndrome
undergoing ovulation induction with clomiphene citrate. Women enrolled in the study will take
50-250 mg of clomiphene citrate on days 3-7 or days 5-9 of their menstrual cycle. They will also
present for transvaginal ultrasound and a serum estradiol levels on menstrual cycle day 12, 13, or
14. Patients will be provided with urinary lutenizing hormone detection kits, and will be
instructed to record the day of their LH surge. Lastly, patients will obtain a serum progesterone
concentration seven days after their LH surge. This data will be organized in a spreadsheet
format. The study participants will then be divided into two groups, those who ovulated and those
who did not. Mean estradiol levels will then be calculated for each group. Appropriate post hoc
statistical analysis will then be performed to evaluate for any correlation between estradiol levels
and ovulation rates.
Progress: A total of 4 patients have enrolled in the study at MAMC during FY06. The study has
been temporarily on hold with COL Proctor's retirement this summer, and I myself (the PI) have
been on an off service rotation and have been unable to consent patients. However, I plan on
adding the REI specialist, COL Chow, to the protocol and starting enrolling new patients shortly.
265
Detail Summary Sheet
Date: 30 Sep 06 Number: 99077 Status: Completed
Title: Misoprostol for the Medical Management of Non-viable First Trimester Pregnancies
Principal Investigator: CPT Jasmine J. Han, MC
Department: OB/GYN Facility: MAMC
Associate Investigator(s): COL Peter E. Nielsen, MC; Troy H. Patience, B.S.; COL Milo L.
Hibbert, MC; MAJ Jason D. Parker, MC; CPT Robert G. Fowers, MC; LTC Louis A. Dainty, MC
Start - Completion: Funding: Periodic Review:
3/9/2000 - Mar 2001 DCI 6/20/2006
Study Objective: The purpose of this study is to examine the effectiveness of Misoprostol
(Cytotec; GD Searle and Co., Chicago, IL) for the management of non-viable first trimester
pregnancies. Specifically, Misoprostol (15-S-15-methyl PGE1) will be compared to a placebo with
expectant management in who have documented non-viable gestations. We will examine the
following outcome variables: time to resolution, number of patients requiring dilation and
curettage, change in hematocrit, cost to the institution, patient satisfaction, and reported side
effects.
Technical Approach: Patients presenting to the OB/GYN clinic with a nonviable gestation,
diagnosis documented by endovaginal ultrasound will be enrolled. Ultrasonic findings will be
verified by two of the resident staff from the obstetrics and gynecology department of Madigan
Army Medical Center. Patients consenting will be directed to the OB/GYN clinic for evaluation,
exam, and counseling and to watch the video giving explanation of purpose of the study and the
planned procedure, but also expected side effects and possible complications. Patients will be
randomized into two groups: study group receiving Misoprostol per vagina and the control group
receiving a placebo per vagina. Subjects will be issued an envelope and go to the pharmacy to pick
up their study medication, blinded to them and the provider. They will also be given Motrin and
Phenergan to help alleviate undesired side effects. Four 200 ug tablets of Misoprostol or placebo
will be placed in the posterior fornix of the vagina using a speculum under the direct visualization
of the provider. Patients will return in 24 hours for re-examination. If no evidence of an
intrauterine pregnancy remains, patients will be informed that their miscarriage was complete,
given precautions and asked to make an appointment for follow-up in 4 weeks in addition to
weekly visits to the lab for quantitative BHCG. All patients will be followed until the quantitative
BHCG has fallen zero to ensure resolution of the pregnancy event.
Patients with evidence of a gestational sac will be given a second dose of Misoprostol or a D&C if
they choose to withdraw from the study or a surgical intervention if it is deemed clinically
indicated by the attending staff. Again, subjects will be given appropriate counseling and
precautions and asked to follow up in an additional 24 hours for re-evaluation. Surveys will be
given at each visit and follow up to evaluate patient satisfaction and also to query for unintended
side effects and complications.
Progress: This protocol completed enrollment during FY06, with thirty patients enrolled, five
during the last 12 months. Data analysis has been conducted and results scheduled for
presentation at an upcoming AFD meeting in October 2006.
266
Detail Summary Sheet
Date: 30 Sep 06 Number: 204111
Status: Ongoing
Title: Glyburide Compared to Insulin in the Management of White's
Gestational Diabetes
Classification A2
Principal Investigator: MAJ Demetrice L. Hill, MC
Department: OB/GYN
Facility: MAMC
Associate Investigator(s): MAJ Andrea D. Shields, MC; LTC Damian J. Paonessa, MC, USAF;
MAJ Jennifer L. Gotkin, MC; LTC Bobby C. Howard, MC, USAF; LTC Peter G. Napolitano, MC;
COL Peter E. Nielsen, MC; CPT Shannon K. Flood, MC
Start - Completion: Funding:
12/14/2004 - Mar 2006 Tripler AMC via MIPR
Periodic Review:
8/22/2005
Study Objective: Pregnant women who meet the diagnostic criteria for gestational diabetes and
fail dietary control will be randomized into two groups. One group will be prescribed glybride and
the other insulin in order to achieve optimal glucose control in pregnancy as manifested by
decreased incidence of large for gestational age fetuses.
Technical Approach: This study will randomize 100 pregnant women into two groups, Group 1
will be prescribed glyburide and Group 2 will be prescribed insulin in order to achieve optimal
glucose control in pregnancy as manifested by decreased incidence of large for gestational age
fetuses. Subjects randomized into standard therapy insulin arm will have their insulin dose
calculated by established standards. Insulin will be adjusted on a weekly basis in order to
maintain optimal glucose control. Women assigned to receive glyburide will begin with 2.5 mg
orally with the morning meal. Glyburide dosage will be increased weekly as indicated by the above
threshold values to a maximum daily dose of 20 mg to achieve glucose control. If maximum daily
dose of glyburide does not result in reaching the threshold values, patients will be administered
insulin; however, data will be analyzed on an intent-to-treat basis. Continuous variables will be
presented as mean +/- standard deviation, ordinal variables as medians, and dichotomous as
percentages. Continuous data with normal distribution will be analyzed using unpaired (2sample)
t-test. For more than 2 samples, analysis of variance (ANOVA, with possible repeated measures)
will be used to analyze differences in outcome. Non-parametric equivalent tests will be used to
compare ordinal variables or continuous variables not normally distributed. Categorical variables
will be compared with the chi-square or Fisher exact test. Odds ratios will be calculated, with 95%
confidence intervals. Logistic regression may be needed to adjust for confounding variables.
Progress: This protocol was closed to enrollment at MAMC due to difficulties with recruitment
(many potential candidates were beyond the 34 week time of diagnosis) and low enrollment. Eight
patients were enrolled; three were randomized to Glyburide and five to insulin. No patients on
Glyburide had adverse reactions; however, two failed Glyburide treatment and were switched to
insulin. This protocol will remain ongoing at MAMC until the protocol is completed at TAMC.
267
Detail Summary Sheet
Date: 30 Sep 06 Number: 206099 Status: Ongoing
Title: Molecular mechanisms of progesterone mediated inhibition of LPS and other
inflammatory agent induced production of pro-inflammatory cytokines in the fetal-maternal
circuitry of the human placenta
Principal Investigator: MAJ Demetrice L. Hill, MC
Department: OB/GYN Facility: MAMC
Associate Investigator(s): LTC Damian J. Paonessa, MC, USAF; MAJ Jennifer L. Gotkin, MC;
CPT Jeremy P. Celver, MS; Heidi M. Cederholm, B.S.; James R. Wright, BA, MT (ASCP); LTC
Peter G. Napolitano, MC
Start - Completion: Funding: Periodic Review:
6/16/2006 - Apr 2007 DCI N/A
Study Objective: To identify the molecular mechanisms by which progesterone modulates pro
inflammatory cytokine production following LPS and other inflammatory agent treatment of cells
and tissue within the fetal/maternal circuit of the human placenta. Analysis will include ELISA,
immunocytochemistry, western, antibody array, and high throughput proteomics.
Technical Approach: Placentas from normal women undergoing elective cesarean delivery prior
to the onset of labor will be obtained within 15 minutes of delivery. At the time of cord clamping,
20cc of fetal cord blood will be obtained, spun down and the white blood cells collected and exposed
to 50mg/ml lipopolysaccharide and evaluated using ID or 2D gel electrophoresis. Additionally,
both umbilical arteries will be gently and thoroughly flushed with Dulbecco's modified Eagle's
medium (Gibco, Grand Island, NY) until the chorionic plate placental arteries are grossly free of
blood. The arteries will be dissected from the placenta, carefully separating connective tissue from
the endothelium. Eight contiguous segments of the umbilical artery (approximately 5 mm each)
will be weighed and cultured in 6-well dishes (four per well) in either Hanks Balanced Salt
Solution (HBSS) or Dulbecco's Modified Eagle's medium with Ham's F12 nutrient mixture (1:1)
(DMEM/F12), antibiotics and 2 mmol/L glutamine in 5% carbon dioxide at 37C. Samples will be
treated with 50ng/mL of lipopolysaccharide, lipopolysaccharide and medroxyprogesterone acetate
(MPA) (50 ng/50 ng/ml), and MPA alone (50 ng/ml). Samples will be screened for total protein
concentration by BCA analysis and specific induction of the inflammatory response by LPS will be
verified with an 116 or IL10 assay. Two placental explants from each group will be snap-frozen in
liquid nitrogen and stored at -130C for possible total cellular proteomic analysis at a later date.
The remaining placental explants will be stored in formalin at 4C and sectioned for
immunohistochemical analyses as necessary.
Total protein from equal volumes of supernatant will be separated by ID or 2D gel electrophoresis
with the assistance of Dr Robert Allen, PhD. Separated proteins will be labeled in gel by
coomassie blue and silver staining. MALDI-TOF (40.00/protein) will be used to identify proteins
with dissimilar expression patterns (e.g., a consistent change between LPS and control in 2/3 of
the tested samples). Immunohistochemistry, western analysis of 2D gels with commercially -
available antibodies and ELISA analysis will validate the proteomic analyses when feasible. A
SELDI-based proteomic analysis will also be considered depending on the effectiveness of the gel
electrophoresis.
Progress: Ten samples have been evaluated. Large variations in the IL-6 production in response
to LPS and LTA have been found. Factors are believed to be technician related. The protocol
continues to collect samples and refine scientific techniques.
268
Detail Summary Sheet
Date: 30 Sep 06
Number: 203067
Status: Ongoing
Title: The Effects of IL-10 on the Production of Inflammatory Cytokine:
Explant Model
s in a Placental Artery
Principal Investigator: LTC Bobby C. Howard, MC, USAF
Department: OB/GYN
Facility: MAMC
Associate Investigator(s): MAJ Andrea D. Shields, MC; MAJ Christine M. Kovac, MC; LTC
Peter G. Napolitano, MC
Start - Completion:
4/30/2003 - Jun 2003
Funding:
Air Force via MIPR
Periodic Review:
4/20/2006
Study Objective: To determine the effects of IL-10 on placental artery production of
inflammatory cytokines from normal patients.
Technical Approach: Maternal-fetal inflammatory states are associated with preterm labor,
preterm premature rupture of membranes, preeclampsia, fetal growth restriction and fetal demise
It is also believed that cerebral palsy results from a fetal inflammatory response characterized by
an environment of pro-inflammatory cytokines. IL-10 is a potent anti-inflammatory cytokine that
has a potential role in the treatment of clinical septicemia by down-regulating the production of
pro-inflammatory cytokines. Approximately 4 specimens will be studied here at MAMC.
Progress: This protocol has not yet initiated enrollment, pending preliminary data from another
study that is currently in data analysis. Modifications may be required prior to initiating
enrollment.
269
Detail Summary Sheet
Date: 30 Sep 06 Number: 203066 Status: Ongoing
Title: The Production of Immunoregulatory Cytokines in a Placental Artery Explant Model
Principal Investigator: LTC Bobby C. Howard, MC, USAF
Department: OB/GYN Facility: MAMC
Associate Investigator(s): MAJ Andrea D. Shields, MC; MAJ Christine M. Kovac, MC; LTC
Peter G. Napolitano, MC
Start - Completion: Funding: Periodic Review:
4/30/2003 - Jun 2003 Air Force via MIPR 4/20/2006
Study Objective: To determine the production of inflammatory cytokines from the placenta
vessels of normal patients following endotoxin stimulation.
Technical Approach: Levels of two distinct cytokines, IL-6 and IL-10 will be determined. IL-6 is
a Th-1 type cytokine that is implicated in cell-mediated damage in clinical states characterized by
an inflammatory response. In contrast, IL-10 is a responsible for down-regulating the TH-1 like
response and has been demonstrated to inhibit the damage related to inflammatory states. By
understanding the production rate of these cytokines by placental arteries at baseline and under
stimulated conditions, it will enable us to study the potential therapeutic modalities to suppress
the production of inflammatory cytokines. Approximately 4 specimens will be examined here at
MAMC.
Progress: This protocol has completed specimen collection with a total of eleven patients
consented in this study. Data analysis is currently ongoing.
270
Detail Summary Sheet
Date: 30 Sep 06 Number: 204088
Status: Ongoing
Title: Use of Transvaginal Cervical Length Measurements in
Principal Investigator: LTC Bobby C. Howard, MC, USAF
Twin Gestations
Department: OB/GYN
Facility: MAMC
Associate Investigator(s): LTC Peter G. Napolitano, MC; Samantha J. Thomas, RN
Start - Completion: Funding:
9/17/2004 - May 2006 DCI
Periodic Review:
5/23/2006
Study Objective: To determine if the use of routine transvaginal cervical length ultrasound can
be used to prevent preterm deliveries in twin gestations.
Technical Approach: Twin gestations are one of the highest risk populations for preterm labor
and ideal to use in this prospective randomized clinical trial to determine if the use of transvaginal
cervical length measures can be used to improve perinatal outcome and prevent unneeded
intervention in women destined to deliver at term. Subjects will be randomized to either routine
management or serial transvaginal ultrasound assessments of cervical length. Subjects
randomized to cervical length assessment will be managed according to a set protocol based on
cervical length. Potential management options will include expectant management, activity
restriction, frequent nursing contact, and/or offering cerclage placement. The primary outcome
analysis will compare gestational age at delivery between groups.
Progress: This protocol closed to enrollment in May 2006, with seven patients enrolled at MAMC,
one during FY06. Data analysis is ongoing.
271
Detail Summary Sheet
Date: 30 Sep 06 Number: 205005 Status: Ongoing
Title: The Distribution of Bishop Scores and Quantitative Values of Fetal Fibronectin (fFN) in
Nulliparous Patients Between 37-42 Weeks Gestation: A Prospective Observational Study
Principal Investigator: CPT Alison L. Lattu, MC
Department: OB/GYN Facility: MAMC
Associate Investigator(s): LTC Bobby C. Howard, MC, USAF; LTC Peter G. Napolitano, MC;
COL Peter E. Nielsen, MC; MAJ Shad H. Deering, MC; Kathleen T. Gardner, RN
Start - Completion: Funding: Periodic Review:
3/11/2005 - Feb 2006 Adeza Biomedical Corp via Geneva Foundation 9/29/2006
Study Objective: To evaluate the distribution of Bishop scores and quantitative values of fetal
fibronectin (fFN) in nulliparous patients between the ages 18 - 40 and between 37 weeks through
42 weeks gestation. The secondary objective is to estimate the predictive value of Bishop scores
and fetal fibronectin (fFN) testing in predicting delivery outcome (e.g. vaginal or cesarean delivery)
in nulliparous patients between 37 weeks through 42 weeks gestation. The third objective is to
compare the concordance and statistical agreement between matched fFN test results collected
with a speculum and fFN tests results collected without a speculum. In this pilot study sample
size is not necessarily sufficient for conclusive results.
Technical Approach: This is a prospective observational clinical study in women between the
ages of 18 through 40. Between 37 weeks through 42 weeks gestation and following verification of
inclusion criteria, fFN testing of cervicovaginal specimen obtained from the lower one-third of the
vagina, fFN testing of a cervicovaginal specimen obtained with a speculum and digital cervical
exam for the evaluation of Bishop score at the time of their routine prenatal visit. All patients
meeting inclusion criteria and who consent to participation will have the following information
recorded: patient's age, gestational age, dating criteria, presentation (and how this was assessed),
fetal fibronectin test results, Bishop score (specifically, cervical dilation, effacement, station,
position, and consistency), and whether or not membrane sweeping was performed. Information
will be obtained regarding the most recent time of intercourse and cervical exam. Following
delivery, the following information about the patient will be obtained: gestational age at time of
admission for delivery, Bishop score (cervical dilation, station, effacement, position, and
consistency) at time of admission, indication for admission, whether labor onset was spontaneous,
induced, or augmented, length of hospital stay, time from admission to delivery, mode of delivery
and birth weight. Additionally, data regarding the presence of the following maternal and fetal
complications will be collected: fetal macrosomia (birth weight >4000gm), pre-eclampsia,
chorioamnionitis, endomyometritis, meconium stained amniotic fluid, NICU admission, and
intrauterine fetal death.
Progress: This protocol remains open to enrollment with 135 patients enrolled to date; 115
patients received diagnostic testing, fourteen were not tested/lost to follow up, three delivered
before testing began, and three withdrew consent. Investigators are currently analyzing interim
data but plan to continue the protocol until full enrollment has been reached. Plan to present some
of the interval data at the annual American College of OB/Gyn Clinical Meeting in May.
272
Detail Summary Sheet
Date: 30 Sep 06 Number: 203078 Status: Ongoing
Title: Use of Pipelle Endometrial Sampling in the Evaluation of Abnormal First Trimester
Pregnancy
Principal Investigator: CPT Alison L. Lattu, MC
Department: OB/GYN Facility: MAMC
Associate Investigator(s): Gregory E. Chow, MD; LTC Michael K. Chinn, MC; CPT Harlan I.
Rumjahn, MC; CPT Joren B. Keylock, MC
Start - Completion: Funding: Periodic Review:
8/27/2003 - Sep 2004 DCI 5/10/2006
Study Objective: To evaluate the sensitivity of endometrial sampling in the detection of
intrauterine products of conception in abnormal gestations.
Technical Approach: This study will look at patients undergoing evaluation and management
for abnormal gestations who have opted for surgical management with dilation and cutterage
(D&C). This will not include patients undergoing emergency procedures. Approximately 100
patients will be enrolled into this study here at MAMC. The patient will have a pipelle
endometrial sampling performed prior to the D&C. This procedure consists of a pipelle being
inserted in to the uterine fundus and drawing it back and forth for 15-30 seconds to obtain a
sample of the endometrial tissue and uterine contents. This sample will be transferred to a 10%
formalin solution and then taken to the pathology department at MAMC for processing and
evaluation.
Progress: Interim data analysis has been completed with sensitivity of EMBX 73% and 92% for
curettage. No adverse outcomes. Investigators will consider whether or not to proceed with
continued enrollment.
273
Detail Summary Sheet
Date: 30 Sep 06 Number: 205089 Status: Ongoing
Title: Pilot Study of a Novel Cord Blood Collection Technique
Principal Investigator: CPT Megan M. Manshande, MC
Department: OB/GYN Facility: MAMC
Associate Investigator(s): MAJ Jasmine T. Daniels, MC; LTC David E. McCune, MC; LTC
Peter G. Napolitano, MC; COL Jerome B. Myers, MC; CPT Mitchel T. Holm, MC; CPT Jeremy P.
Celver, MS; Carol D. Dean, RN, BSN
Start - Completion: Funding: Periodic Review:
5/26/2005 - Apr 2006 DCI 5/22/2006
Study Objective: Primary Objective: To demonstrate the feasibility of a novel technique for
umbilical cord blood collection after delivery. Secondary Objective: To compare this method of
collection to historical results obtained from medical literature.
Technical Approach: After collecting umbilical cord blood via the method proposed in this
protocol, investigators will compare blood volumes and the number of hematopoietic progenitor
cells harvested to historical controls. Investigators propose that this new method of cord blood
collection after delivery will allow collection of a larger volume of umbilical cord blood than the
currently used standard method of cord blood collection thus allowing harvest of a larger number
of stem cells. Development of a collection technique which would give a higher yield of stem cells
would broaden the range of transplant options available for adult recipients.
Progress: Investigators have now obtained the proper equipment kits to collect samples and will
have all samples collected within the next two months. Two patients were enrolled in the study
since its approval, but will not be included in the final data because investigators were perfecting
the collection technique prior to actually collecting samples to include in the study.
274
Detail Summary Sheet
Date: 30 Sep 06 Number: 203045 Status: Ongoing
Title: Randomized Controlled Trial of Endurance Exercise and Gallbladder Disease Risk in
Overweight Pregnant Women
Principal Investigator: ETC Peter G. Napolitano, MC
Department: OB/GYN Facility: MAMC
Associate Investigator(s): Sum P. Lee, M.D., Ph.D; Shirley Beresford, Ph.D; Cynthia Ko,
M.D.; Anne McTiernan, M.D.; Deborah J. Bowen, Ph.D; LTC James K. Howden, MC; COL Peter
E. Nielsen, MC; Scott J. Schulte, M.D.; Mary Emond, Ph.D
Start - Completion: Funding: Periodic Review:
1/27/2004 - Jan 2008 UW via The Geneva Foundation 1/24/2006
Study Objective: (1) To evaluate whether an endurance exercise program is associated with
lower risk of gallbladder disease in overweight pregnant women. (2) To evaluate whether an
endurance exercise intervention program changes leptin levels in pregnancy among overweight
women. (3) To use statistical methods to examine the associations between gallbladder disease
incidence and potential causal variables in this prospective trial. These variables include baseline
levels of leptin, HDL, insulin levels, BMI (as it varies within women classified as overweight) and
changes in these variables. Secondarily, we aim to estimate the degree of compliance and overall
adherence to an exercise intervention in normal weight pregnant women, in the context of a
randomized intervention study.
Technical Approach: This trial will evaluate the effect of an intervention designed to increase
regular endurance exercise of moderate to vigorous intensity on the risk of gallbladder disease in
pregnancy.. Women will be stratified according to overweight or normal weight status. The
randomized controlled trial will be confined to the former group (n=862), while a feasibility trial
will be conducted among 250 normal weight women. The comparison groups will receive the
exercise intervention in the post-partum period. They will continue their usual activities during
pregnancy. Thus all women participating in the trial will receive the benefit of exercise training at
some point during the study period. The study population will be pregnant women aged 18 to 45.
All women presenting for prenatal care will be potentially eligible. Additional clinical procedures
specific to the study include a first and third trimester ultrasound of both the gallbladder and the
fetus, and an additional blood draw at those times. Usual care includes a second trimester
ultrasound of the fetus, to which will be added an ultrasound of the gallbladder, and a blood draw,
to which additional tubes will be added. To enhance cooperation with additional study procedures
in the exercise intervention study, we will provide a $30 financial incentive for completing the 1st
trimester and late 3rd trimester blood draws. This incentive will not be provided for the early 3rd
trimester blood draw, since it occurs at the same time as a routine prenatal blood draw. As an
added incentive to participate, an additional scan of the fetus will be made at the first trimester
gallbladder ultrasound examination. This will allow women an early glimpse of their baby. For
women who have other children, we will provide a reimbursement for childcare expenses ($3 per
hour) during exercise or stretching classes. Pedometers will be provided during the study for the
intervention group, and at the postpartum visit for the control women.
Progress: This protocol remains open to enrollment, with 3,707 women contacted, 846 women who
agreed to enroll and 443 who completed the study. Of this group, 204 were disqualified because of
gallstones, miscarriage or failure to comply with study requirements/medical conditions.
Expanding the BMI range to 34.9 has allowed enrollment of 38 additional women that would not of
qualified.
275
Detail Summary Sheet
Date: 30 Sep 06 Number: 203001
Status: Ongoing
Title: The Effect of Magnesium on Matrix Metalloproteinase-9 Activity in
at Delivery of Pregnancies Complicated by Chorioamnionitis
Umbilical Cord Blood
Principal Investigator: ETC Peter G. Napolitano, MC
Department: OB/GYN
Facility: MAMC
Associate Investigator(s): CPT Patrick M. McNutt, MS; Lisa M. Pierce, D.Sc.; MAJ Christine
M. Kovac, MC; LTC Bobby C. Howard, MC, USAF; MAJ Brian T. Pierce, MC; LTC Nathan J.
Hoeldtke, MC
Start - Completion: Funding:
7/29/0030 - Dec 2002 DCI
Periodic Review:
9/21/2006
Study Objective: To determine baseline umbilical cord serum levels of matrix metalloproteinase-
9 levels at delivery in pregnancies where labor is complicated by chorioamnionitis compared to
normal term controls. To determine if magnesium will reduce the enzymatic activity of serum
matrix metalloproteinase-9 in the umbilical cord plasma of neonates from pregnancies complicated
by chorioamnionitis compared to normal controls.
Technical Approach: Matrix metalloproteinases are zinc-dependent enzymes and it is possible
that ionized magnesium which easily crosses the placenta could competitively inhibit MMP-9
enzyme by displacing zinc. We propose to test this hypothesis by first determining what normal
levels of MMP-9 enzyme are in pregnancies complicated by infection (those complicated by
chorioamnionitis in labor) compared to normal pregnancies with normal labors. Since it would not
ethically be acceptable to administer Magnesium sulfate a tocolytic to such complicated
pregnancies, we will collect the plasma of such pregnancies then expose it ex vivo to similar levels
of magnesium that would be expected if we had treated the mother with standard therapy. Then
assay those samples for MMP-9 enzyme activity.
Progress: Bench top research completed, paper submitted but rejected, and awaiting changes to
be made and resubmission. This study remains open as investigators may need to collect more
specimens, based on peer review of findings.
276
Detail Summary Sheet
Date: 30 Sep 06 Number: 203099
Status: Ongoing
Title: Umbilical Cord Plasma Homocysteine Concentrations at Delivery in Pregnancies
Complicated by Preeclampsia
Principal Investigator: ETC Peter G. Napolitano, MC
Department: OB/GYN
Facility: MAMC
Associate Investigator(s): CPT Christopher S. Murphy, MC;
CPT Charles L. Wakefield, MC
Start - Completion: Funding:
8/1/2003 - Dec 2003 DCI
Periodic Review:
6/20/2006
Study Objective: The purpose of this study is to evaluate the level of umbilical cord plasma
homocysteine in gestations complicated by pre-eclampsia compared to normotensive gestations.
Technical Approach: General Protocol Sampling Umbilical cord blood samples will be obtained
immediately after cord clamping by direct venipuncture of the umbilical vein collected in lavender
top tubes. The specimens will be stored on ice and centrifuged at 3000 rpm for 15 min as soon as
possible. After extracting the serum plasma, it will be divided into several aliquots for storage. All
specimens will be frozen and maintained at -70o C. Maternal plasma obtained at the time of
routine labor admission blood work will be collected and stored in a similar fashion. At four points
during the study, the specimens will be collected and sent to William Beaumont Army Medical
Center, TX, Dept of Pathology for homocysteine level analysis. A sample of lmL of EDTA plasma
is necessary for laboratory analysis. The plasma homocysteine level is measured by AD VIA
Centaur HCY assay. Each specimen will be run in duplicate.
Progress: This protocol remains open to enrollment. No new patients were enrolled since the last
progress report. The protocol was amended to allow inclusion of patients with Preterm
preeclampsia and Preterm preeclampsia with IUGR, although recruitment of patients did not
occur. Recruitment and enrollment is expected to begin with the addition of a new associate
investigator, Dr Christopher Murphy. At this time, data analysis has been performed on ten
control patients and eight patients with pre-eclampsia. There was a significant difference between
HCY levels in the pregnancies complicated by pre-eclampsia and the control patients (maternal
and fetal).
277
Detail Summary Sheet
Date: 30 Sep 06 Number: 204108 Status: Completed
Title: The Effects of Cholic Acid and Deoxycholic Acid on Placental Artery Perfusion Pressures
in the Ex Vivo Placental Cotyledon Model
Principal Investigator: ETC Damian J. Paonessa, MC, USAF
Department: OB/GYN Facility: MAMC
Associate Investigator(s): LTC Nathan J. Hoeldtke, MC; LTC Peter G. Napolitano, MC; LTC
Bobby C. Howard, MC, USAF; MAJ Andrea D. Shields, MC; MAJ Jennifer L. Gotkin, MC
Start - Completion: Funding: Periodic Review:
8/31/2004 - May 2005 Air Force via MIPR 8/22/2005
Study Objective: To determine if infused concentrations of cholic acid and deoxycholic acid affect
placental artery perfusion pressures.
Technical Approach: This bench study will evaluate the placental vascular tone after exposure
to the bile salts cholic acid and deoxycholic acid. Placentas from normal women will be obtained
within 15 minutes of delivery. Fetal surface will be inspected for a chorionic artery and vein pair
supplying a functional cotyledon. Although wavier of informed consent was appropriate,
investigators chose to utilize a consent form to obtain permission for use placentas under this
bench research protocol.
Progress: The PI reported this protocol completed in June 2006; he is in the process of data
analysis. Nine placentas were collected; three did not survive the attempt to collect data.
278
Detail Summary Sheet
Date: 30 Sep 06 Number: 205021 Status: Ongoing
Title: Correlation of Persistent Anal Sphincter Defects and Symptoms following Repair of Anal
Sphincter Lacerations due to Obstetric Injury in Primiparous Women
Principal Investigator: CPT Christine M. Zalucki, MC
Department: OB/GYN Facility: MAMC
Associate Investigator(s): LTC Jeffery L. Clemons, MC; CPT Rhiana D. Saunders, MC
Start - Completion: Funding: Periodic Review:
12/10/2004 - Jan 2005 DCI 11/21/2006
Study Objective: To identify the incidence of persistent anal sphincter defects following repair of
anal sphincter lacerations (ASL) due to obstetric injury in primiparous women. To correlate the
size of the persistent anal sphincter defect (ASD) with anal incontinence symptoms. To identify the
size of ASD at which symptoms increase dramatically, if any. To identify risk factors for
symptomatic ASD.
Technical Approach: A prospective observational study will be conducted over a 24 month
period. Primiparous women that have sustained an ASL and undergone successful repair will be
recruited during their postpartum stay at MAMC. Obstetric records will be reviewed to collect
demographic data, medical history, delivery outcomes, and anal sphincter repair technique. At 8
weeks postpartum, each woman will undergo endoanal sonography and complete the Wexner anal
incontinence questionnaire. The endoanal ultrasound will be used to detect and measure the size
of ASD. A persistent ASD will be defined as any defect of the integrity of the IAS or EAS.
Photographic images will be taken of the largest portion of the ASD. The size of the defect (in
degrees) will be measured by a protractor. The length of the defect (in millimeters) will be
measured by 3-D ultrasound. Three researchers will perform all measurements. The
endosonographer will be blinded to the questionnaire results. The Wexner anal incontinence
questionnaire assesses the presence and frequency of incontinence to flatus, liquid and solid stool,
pad use, and lifestyle alteration. Scores can range from 0 (complete continence) to 20 (severe
incontinence to solid stool on a daily basis). A score of 4 or more at 2 months post-partum will
define a symptomatic ASD. Women with and without symptomatic ASD will be compared to
identify risk factors for symptomatic ASD. Approximately 72 women with ASD will be needed to
demonstrate a difference in defect size between symptomatic and asymptomatic ASD.
Demographic and delivery data will be entered onto a Data Sheet. The ultrasound data and
questionnaire data will be also entered onto the Data Sheet. All data will then be transferred to
the Excel spreadsheet. Security issues will be enforced (locking computer and office).
Progress: This protocol completed the enrollment phase with a total of 47 patients enrolled at
MAMC over the 20 month enrollment period. Patients will continue to be followed by phone
through FY07. The study found that an injury to the internal anal sphincter > or = 45 degrees was
strongly associated with anal incontinence symptoms. Also, the anal sphincter laceration rate at
MAMC is 3%, and persistent defect rate is 79%. No risk factors were identified for persistent anal
sphincter defects. One patient underwent overlapping sphincteroplasty for severe anal
incontinence.
279
Detail Summary Sheets
Department of Pathology
280
Detail Summary Sheet
Date: 30 Sep 06 Number: 203095 Status: Terminated
Title: Implementation of the SARS Coronavirus Real-Time PCR Primers and Probes Assay to
Detect SARS Coronavirus in Respiratory Specimens
Principal Investigator: MAJ Edward P. Ager, MS
Department: Pathology Facility: MAMC
Associate Investigator(s): MAJ Steven D. Mahlen, MS; COL Joseph T. Morris III, MC; LTC
David K. Turgeon, MC; LTC James E. Cook, MC; CPT Sheryl A. Bedno, MC
Start - Completion: Funding: Periodic Review:
5/12/2004 - Jul 2004 CDC via MIPR 7/1/2005
Study Objective: To use real-time PCR assays to detect SARS Coronavirus RNA in respiratory
specimens and as a surveillance tool allowing public health laboratories to respond to the outbreak
and limit transmission of this agent.
Technical Approach: This protocol describes a plan to export the current CDC SARS
Coronavirus real-time PCR assay to participating public health laboratories and clinical diagnostic
laboratories within the Laboratory Response Network (LRN) for use in diagnostic evaluation of
SARS Coronavirus infection. Fifty patients will be enrolled for this protocol, and two sets of
specimens will be taken from each subject. One set of specimens will be shipped to the CDC for
testing; the other set of specimens will be tested for the SARS Coronavirus at MAMC. SARS
Coronavirus detection data will be collected for this study, and compared with results obtained
from the CDC.
Progress: A change PI was approved from MAJ Steven Mahlen, MS, to MAJ Edward Ager, MS,
Staff Department of Pathology. The protocol was terminated 15 May 2006, with no subjects
enrolled. No human infection with the SARS coronavirus was identified in over 2 years.
281
Detail Summary Sheet
Date: 30 Sep 06 Number: 203041 Status: Ongoing
Title: Use of a Non-FDA Approved Gene Amplification Test To Detect or Rule-Out Vaccinia in
Patients With Complications Following Smallpox Vaccination or Possible Contact Vaccinia
Principal Investigator: MAJ Edward P. Ager, MS
Department: Pathology Facility: MAMC
Associate Investigator(s): MAJ Steven D. Mahlen, MS; COL Joseph T. Morris III, MC; COL
Mary P. Fairchok, MC; LTC Peter G. Napolitano, MC
Start - Completion: Funding: Periodic Review:
4/30/2003 - Mar 2004 DCI 7/20/2006
Study Objective: To determine the sensitivity, specificity and clinical utility of the only test
currently available to detect vaccinia virus in patients who may be experiencing post-vaccination
complications following smallpox vaccination, or in close contacts of vaccinees who may have been
inadvertently inoculated with the vaccinia virus (contact vaccinia).
Technical Approach: Clinicians seeing patients with possible post-vaccination complications or
suspected contact vaccinia will collect and submit three swabs of lesion fluid to one of the DOD
Confirmatory Labs with the vaccinia test. One swab will be used for vaccinia PCR using either the
Cepheid SmartCycler or the Idaho Technology LightCycler platforms that are approved as LRN
tools. DNA extraction and amplification will be done strictly following the LRN protocol.
Extraction of DNA from exudate material and specimen processing will take approximately 2
hours. Amplification results will be final approximately 30 minutes after the amplification begins.
A positive amplification result is determined by standardized parameters and with a calculated
threshold done by the real-time PCR unit. The second swab will be used for viral culture. Vaccinia
virus produces cytopathic effects (CPE) in most common cell lines used in clinical virology labs.
The CPE resemble those of HSV, CMV and adenovirus. While clinical labs can rapidly identify
HSV, adenovirus and CMV in infected cell lines using DFA, there is no such test for vaccinia.
However, if a specimen results in CPE, but is negative for HSV, adenovirus and CMV by DFA,
then that culture may be a presumptive result for vaccinia, and will be resulted as "CPE from
lesion material - negative for HSV, adenovirus, and CMV". Specimens with no resultant CPE will
be finalized as "No virus detected". The third swab will be submitted for bacterial culture and
sensitivity (standard of care). Viral and bacterial culture data, along with PCR data will be used
in conjunction with the clinical situation to help determine if the patient has post-vaccinial
complications due to vaccinia virus, contact vaccinia, or is experiencing rashes or lesions due to
other causes. All specimens kept at the DOD LRN Confirmatory Labs will be handled and
disposed of in accordance with federal regulations.
Progress: This protocol remains open to patient entry, with six patients enrolled, one during
FY06. This is a CDC Protocol and as such is conducted under auspice of the CDC IRB.
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Detail Summary Sheet
Date: 30 Sep 06 Number: 205102 Status: Ongoing
Title: Absolute Lymphocytosis in Adults: A Laboratory Protocol
Principal Investigator: CPT Jared M. Andrews, MC
Department: Pathology Facility: MAMC
Associate Investigator(s): CPT Mitchel T. Holm, MC; COL Jerome B. Myers, MC
Start - Completion: Funding: Periodic Review:
7/12/2005 - Oct 2005 DCI 6/12/2006
Study Objective: The objective is to analyze and report correlations between diagnosis rendered
by flow cytometry analysis of patients with peripheral blood lymphocytosis, and the lymphocyte
counts and other demographics of the patients. International guidelines for flow cytometric
analysis of peripheral blood lymphocytosis to rule out leukemia/ lymphoma are not well defined.
These correlations can be used to help develop hospital protocols for the evaluation of absolute
lymphocytosis in adults.
Technical Approach: This is a retrospective, descriptive study of Madigan Army Medical
Center's process for analysis of peripheral blood lymphocytosis in persons greater than 18 years of
age. By analyzing the demographic data, CBC, and flow cytometrical results obtained, it is our
hypothesis that this information can be beneficial in more accurately defining guidelines for the
use of flow cytometry for lymphocytosis, and promote further prospective research in this area.
Progress: This protocol has completed data collection and statistical analysis and remains
ongoing to complete final manuscript of findings.
283
Detail Summary Sheet
Date: 30 Sep 06 Number: 205042
Status: Ongoing
Title: Incidental Anatomic and Histologic Findings in Bariatric Surgery Specimens
Principal Investigator: MAJ Anne L. Champeaux, MC
Department: Pathology
Facility: MAMC
Associate Investigator(s): MAJ James B. Branch, MC;
CPT Vance Y. Sohn, MC
Start - Completion: Funding:
2/14/2005 - Apr 2005 DCI
Periodic Review:
10/26/2006
Study Objective: Collection, review and compilation of anatomic/histologic findings in bariatric
surgery specimens processed by Madigan Army Medical Center (MAMC) Department of Pathology,
Anatomic Pathology Service from 1994-2004.
Technical Approach: Collection, review and analysis of bariatric surgery specimen reports
generated by the MAMC Anatomic Pathology service from 1994 through 2004 to identify and
correlate anatomic and histologic findings with age and gender. The study aims to elucidate the
range of anatomic and histologic variables found in partial gastrectomy, gallbladder and
appendices removed during bariatric procedures.
Progress: This protocol was suspended in February 2006, pending completion of the continuing
review process. PI intends to request IRB approval to increase the number of patient cases and
records up to 600 and add an associate investigator.
284
Detail Summary Sheets
Department of Pediatrics
285
Detail Summary Sheet
Date: 30 Sep 06 Number: 203014 Status: Terminated
Title: Clinical Use of Reticulocyte Hemoglobin to Detect Iron Deficiency at the 12 Month Well
Baby Visit
Principal Investigator: CPT Rochelle L. Cason, MC
Department: Pediatrics Facility: MAMC
Associate Investigator(s): CPT Athena J. Stoyas, MC; LTC Robert G. Irwin, MC; COL Kelly J.
Faucette, MC; Elizabeth N. Hasert, MD
Start - Completion: Funding: Periodic Review:
3/4/2003 - May 2003 DCI 9/28/2004
Study Objective: To determine if the reticulocyte hemoglobin is a more sensitive and specific
marker than hemoglobin and hematocrit for iron deficiency at the 12 month well child visit.
Technical Approach: This is a prospective study that will evaluate the utility of reticulocyte
hemoglobin as a screen for iron deficiency and iron deficiency anemia in comparison to current
measures of hemoglobin and hematocrit. All infants that present for their 12 month well child
check and any infants 9 to 18 months with a clinical indication or who have missed their 12 month
well baby visit will have screening hemoglobin, hematocrit, and reticulocyte hemoglobin. If either
hemoglobin, hematocrit, or reticulocyte hemoglobin are low these patient's will be placed on iron
therapy. The three treatment groups will include: 1. Decreased hemoglobin, hematocrit, and
reticulocyte hemoglobin; 2. Decreased hemoglobin and/or hematocrit. Normal reticulocyte
hemoglobin; 3. Normal hemoglobin and hematocrit. Decreased reticulocyte hemoglobin. After one
month of therapy a repeat venous hemoglobin, hematocrit, and reticulocyte hemoglobin will be
checked. If these measurements show improvement as previously defined, the patient will be
diagnosed with iron deficiency and/or iron deficiency anemia and will continue on two more
months of iron therapy. Measurements of hemoglobin and hematocrit and reticulocyte hemoglobin
will be compared in their sensitivity and specificity in detecting iron deficiency and iron deficiency
anemia. If group 1 shows improvement in all tested variables, this would suggest that reticulocyte
hemoglobin correlates well with hemoglobin and hematocrit measurements. If group 3 responds to
therapy and group 2 does not respond to therapy this would indicate that reticulocyte hemoglobin
is a more sensitive and specific indicator of iron deficiency. 60 patients will be placed into each
group. Once 30 patients are in each group an interim analysis, using chi square, of the data will be
obtained to assess if there is statistical significance.
Progress: The IRB terminated this protocol in August 2006, when no principal investigator was
assigned by the Department of Pediatrics during the study's last approval period. The protocol had
been suspended at the request of associate investigator, Dr. Hasert, until a new PI could be
assigned. The last report noted 57 of 500 patients enrolled with 7 positive results that support the
study hypothesis.
286
Detail Summary Sheet
Date: 30 Sep 06 Number: 204104
Status: Ongoing
Title: Health, Quality of Life & Activity in Cerebral Palsy
Principal Investigator: COL Beth E. Davis, MC
Department: Pediatrics
Facility: MAMC
Associate Investigator(s): MAJ Robert L. Miller, MC; Kristie Bjornson, PhC, PT
Start - Completion: Funding:
9/13/2004 - Jun 2006 United Cerebral Palsy Research & Education
Foundation via Grant
Periodic Review:
8/10/2006
Study Objective: Aim 1. To test for differences in activity performance, self and parent reported
health status and QOL (Quality Of Life) among youth with CP (Cerebral Palsy) and TDY
(Typically Developing Youth) by level of activity capacity, while controlling for baseline activity
performance and capacity, age, gender, SES and current day outlook. The predicted differences in
activity performance, self-reported health status will be such that TDY will be greater than CP
youth (TDY > CP), and that these differences will be ordered by defined levels of activity capacity
with the Gross Motor Function Classification System (GMFCS) such that TDY > Level I > Level II
> Level III, while controlling for baseline activity performance, age, gender, SES and current day
outlook. The predicted differences in QOL will not be ordered by activity capacity.
Aim 2. To examine the associations between activity level (performance) and self and parent
perceived health status and QOL in youth with CP and TDY, while controlling for baseline activity
performance and capacity, age, gender, SES and current day outlook. There will be a positive
linear relationship by activity capacity level (GMFCS) between activity performance and the
health status physical domain (Child Health Questionnaire, CHQ-P). There will be a positive
linear relationship by activity capacity (GMFCS) between activity performance and the QOL
relationship domain (Youth Quality of Life, YQOL-R). The relationship of activity performance to
the health status psychosocial domain (CHQ-PS) and the QOL self, environment and general QOL
(YQOL-R: S, E & GQOL) will not be linear by activity capacity level.
Aim 3. Explore a model specifying the influence of activity capacity and activity performance on
health status and quality of life controlling for baseline activity performance, age, gender, SES,
and current day outlook.
Technical Approach: This is a multi-center study that intends to study the health, quality of
life, and activity in children with cerebral palsy. Children with the diagnosis of cerebral palsy,
Gross Motor Function Classification System (GMFCS) levels I-III and typically developing youth,
ages 10 to < 14 years, with the ability to read and understand at the 10 year age level will be
studied. 30 children with cerebral palsy and 10 children that are typically developing that meet
inclusion criteria through the MAMC study site will be enrolled, as well as one parent/guardian of
each child enrolled (40 parents). Potential study participants will be recruited through a focused
direct mailing of an approach letter introducing the project to the guardians of children with CP
and typically developing youth that have had medical care at the MAMC Developmental
Pediatrics, General Pediatrics, and Family Practice clinics. An informational letter will be sent to
school based nurses, physical and occupational therapists, or other health care providers at
military facilities in Western Washington. The letter will introduce the project, state that
ambulatory children with CP and TDY are being sought for participation in the study, the
inclusion criteria and brief description of the project. Local health care providers can then
approach their patients about interest in the study and give them the contact information of the PI
and/or contact the PI for further information about the project.
287
Once consent and assent have been attained, there will be two research visits seven days apart in
the participants' home at their convenience. At the first visit, the youth will be asked to complete
the questionnaires and have the Step Watch calibrated to their walking pattern. They will be
asked to wear the Step Watch for seven days. On day seven, researchers will return to their home
to download the information from the Step Watch and complete appropriate questionnaires.
Parents/ guardians will be asked to complete the appropriate questionnaires on visit day one and
visit day seven. For specific primary and secondary outcomes, design and procedures, data
preparation, and analysis, see sections 9.3 through 9.6 in the Master Protocol.
Progress: Data collection was completed for twenty MAMC subjects, sixteen during FY06. Data
collection continued for subjects in specific categories of impairment related to their CP from the
CHRMC research office, for a total of over 100 patients with cerebral palsy. This was completed in
December 2005. Data analysis began and Principal PI at CHRMC (K. Bjornson) defended PhD
dissertation with results. The protocol remains ongoing at MAMC. Initial manuscript preparation
underway regarding the scope of activity recorded for varying degrees of physical impairment in
children with cerebral palsy.
288
Detail Summary Sheet
Date: 30 Sep 06 Number: 204074
Status: Ongoing
Title: Survey of Chronic Pain and Its Effects on Youth With Disabilities
Principal Investigator: COL Beth E. Davis, MC
Department: Pediatrics
Facility: MAMC
Associate Investigator(s): Joyce M. Engel, PhD, OTR/L; Kenneth M. Jaffe, M.D.; John F.
McLaughlin; Mark P. Jensen, PhD; Dawn Ehde, PhD
Start - Completion: Funding:
Periodic Review:
6/16/2004 - May 2007 DCI
8/10/2006
Study Objective: This study has two specific aims: (1) to increase our understanding of the
frequency and severity of pain problems in youth with spina bifida (SB), muscular dystrophy (MD),
cerebral palsy (CP), limb deficiency (LD), and spinal cord injury (SCI); and (2) to develop a
biopsychosocial model for the study of chronic pain in youth with disabilities.
Technical Approach: This study uses a cross sectional design. A convenience sample of 100-150
youths will be interviewed in-person or over the telephone to complete a standardized
questionnaire on pain. The youths' parent/guardian will also be invited to complete a
questionnaire (assistance will be provided as needed). Subject inclusion criteria include: a primary
diagnosis of CP, LD, SCI, SB, or MD, a chronological age range of 8-to-20 years, capacity for
expressive communication which may include the use of augmentative communication devices,
English as the primary language, and no more than mild cognitive impairment. Subjects will be
paid $40.00 ($25.00 for youth and $15.00 for parent/guardian) for the completion of
interview/questionnaire. Potential subjects will first be contacted directly by Dr. Beth Ellen Davis
or medical personnel involved in the care of the youths, via an approach letter mailed by Dr. Davis,
or posting of a recruitment flyer . Parents/guardians and young adults who are interested in the
study will be asked to return an interest/information form in the provided postage-paid envelope to
Dr. Davis at the Developmental Pediatrics Clinic at Madigan Army Medical Center. Dr. Davis will
then inform UW investigators via confidential e-mail, a letter sent through the mail or telephone
calls of those families interested in participating. UW research personnel will then contact these
potential subjects. Interested parents/guardians or youth may also contact the principal
investigator or study project director via e-mail or telephone. At the time of the contact, the
purpose and procedures of the study will be explained and the parent/guardian will have the
opportunity to ask questions. If the parent/guardian and youth express interest in the
participating in the study, the investigator will screen to insure that all inclusion criteria have
been met including a brief cognitive screening. If the inclusion criteria are met, an interview will
be scheduled at a time and place (University of Washington Medical Center, the subject's home, or
over the telephone for youths without speech difficulties) that is most convenient for the subjects.
Assent and consent forms will be completed by the youth and parent/guardian prior to the
initiation of the interview/questionnaire. A brief, standardized cognitive screening will also be
completed prior to initiation of the interview (youth subject must score a minimum of 17/25 on the
modified Mini Mental Status Examination to be eligible for participation. A subject descriptive
information sheet will be completed. The youth will then be interviewed in-person or over the
telephone by a study investigator or trained research assistant while the parent/guardian
completes a disability specific form and a written questionnaire. The youth's interview and
parent/guardian questionnaire each will take approximately 10 to 50 minutes to complete
depending on whether or not the youth reports recurrent, bothersome pain. Response keys are
used throughout the interviews to facilitate answering questions. All data will be entered into MS
ACCESS. After all data have been entered, variables will be inspected for outliers and skewness
and adjusted using appropriate transformations. Descriptive analysis will then be performed.
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Progress: In the last year, 36 dyads (parent and youth with spina bifida) have completed various
(11) comprehensive surveys regarding pain and its effects on daily living. An abstract describing
the early results of the nature and scope of pain in youth with spina bifida was accepted for
presentation at two national meetings: Poster presentation at AACPDM, Orlando Fla. 15 Sep
2005; research competition at the AAP Uniformed Services Pediatric Seminar, Portsmouth VA,
March 13, 2006 where it came in Second Place in the military peer reviewed Margilith Research
Award. Overall, descriptive information revealed that recurrent bothersome pain is common in
youths with SB. Despite effectiveness of non-medical interventions, most participants reported use
of opiates/narcotics as most helpful for their chronic pain symptoms. Manuscript preparation is
underway. The protocol remains ongoing; the next step is to analyze the Quality of Life data with
the reported pain frequency, intensity and locations.
290
Detail Summary Sheet
Date: 30 Sep 06 Number: 206049 Status: Ongoing
Title: An Observational Study to Determine the Factors Influencing Bone Mineral Density in
Post-Menarchal Adolescents with Neuromuscular Disabilities
Principal Investigator: MAJ Michelle K. Ervin, MC
Department: Pediatrics Facility: MAMC
Associate Investigator(s): COL Beth E. Davis, MC; LTC Stephen M. Yoest, MC; COL (Ret)
Patrick C. Kelly, D.O.; LTC Antonio G. Balingit, MC
Start - Completion: Funding: Periodic Review:
3/7/2006 - Jun 2007 DCI N/A
Study Objective: To determine bone mineral density measurements by use of DEXA technique at
the distal femur, in a heterogeneous group of post-menarchal females with neuromuscular
disabilities and compare to previously published reference data of age-matched normal controls. To
describe the associations between bone mineral density measurement and multivariate factors
such as: 1) anti- epileptic medication use, (2) mobility status as defined by the Gross Motor
Function Classification System (GMFCS; see appendix for description of this scale), (3) Body mass
index (BMI), (4) Tanner staging, and (5) hormonal contraceptive use while controlling for
nutritional intake, specifically calcium and vitamin D.
Technical Approach: This observational pilot study will evaluate the bone mineral density in a
heterogeneous group of 45 post-menarchal females ages 11 through 24 with neuromuscular
disabilities that meet the inclusion criteria. The change in bone mineral density will be
descriptively compared. Potential subjects will be recruited through a focused direct mailing of an
approach letter introducing the project to the subject and/or guardians of eligible adolescent
females receiving care at the Madigan Army Medical Center Pediatric Clinic, Adolescent Clinic,
and Developmental-Behavioral Clinic. The letter will introduce the project, and state that post-
menarchal females with neuromuscular disabilities are being sought for participation in the study,
the inclusion criteria and a brief description of the project. Once consent, assent or surrogate
consent has been obtained, a clinic appointment will be scheduled with a member of the
investigative team to conduct an intake history and physical exam, and initiate dietary
assessment through the use of a three day diet diary. Those participants identified as having
insufficient calcium and/or vitamin D intake will be provided with supplemental therapy. Subjects
will have distal femur bone mineral density measured at baseline, 6 months and 12 months. No
current reference normative data exists for this population. Once all of the data is collected BMD
measurements will be descriptively compared using multivariate logistical regression to determine
significance of osteopenia risk factors identified for each subject.
Progress: This protocol remains open to enrollment, with 18 subjects enrolled during FY06. All 18
subjects completed the initial baseline bone mineral density scan, and one patient has returned for
the six- month interval scan. The study staff is currently in the process of scheduling six- month
interval scans for the remaining 17 subjects. The IRB recently approved an amendment to include
a lumbar spine DEXA, along with the already approved distal femur DEXA when subjects return
for their six- month and twelve-month follow up visits. One study patient died; however, this death
was considered unrelated to study participation. Patient follow-up visits and study recruitment
will continue during FY07.
291
Detail Summary Sheet
Date: 30 Sep 06 Number: 205138
Status: Ongoing
Title: Evaluation of Serologic Responses to Fluzone® in Infants > 6 Months of Age Who Did or
Did Not Receive Fluzone Vaccine at 2 Months of Age
Principal Investigator: COL Mary P. Fairchok, MC
Department: Pediatrics
Facility: MAMC
Associate Investigator(s): Sue E. Chambers, RN
Start - Completion: Funding:
11/17/2005 - Sep 2006 Sanofi Pasteur via The Geneva Foundation
Periodic Review:
9/26/2006
Study Objective: To demonstrate the safety and immunogenicity of Fluzone vaccine
administered in 6 month olds who have previously received this immunization compared to 6
month olds who have not received this vaccine previously.
Technical Approach: This is an observational and descriptive study that will provide
preliminary comparative information about the safety and immunogenicity of Fluzone vaccine
among children who were given Fluzone vaccine at 2 months of age as part of MAMC protocol
205034 (Group 1) versus children who have never received influenza vaccine (Group 2). All
participants will be enrolled after obtaining informed consent from their parent or guardian.
At study visit 1, all participants will undergo informed consent, and a medical history and directed
physical exam will be conducted. All participants will then receive one 0.25 mL intramuscular
injection of Fluzone®. Both groups will be provided with a diary card to take home at this visit,
recording solicirted and unsolicited local and systemic adverse effects of the vaccines as well as
daily temperatures for the 7 days after the visit.
At study visit 2, a blood sample will be collected from all subjects, and both groups will receive a
second 0.25ml intramuscular injection of Fluzone®. Interim histories and diary cards will be
collected and a second diary card will be provided.
At study visit 3, a blood sample will be collected from all subjects. Diary cards and interim history
will be obtained. There will be a follow up contact by phone of all study participants at 6 months
after visit the last dose of Fluzone® to solicit adverse events.
Other, non- study, vaccinations may be given at any study visit or at any time beginning 15 days
following Visit 2. No vaccinations may be given between Visit 1 and Visit 2, nor in the 14 days
preceding Visit 1 or following Visit 2.
Outcome variables for safety include 1. Frequency and percentage of subjects who had solicited
injection site and systemic reactions 2. Frequency of subjects reporting medically attended
unsolicited adverse events and serious adverse events and the frequencies of these events
Outcome variables for immunogenicity include 1. Post-vaccination seroprotection rates: the
proportion of subjects with HAI titers (? 1:40) for influenza strains following each vaccination.
2. Post-vaccination geometric mean of anti-HAI titers for influenza strains following each
vaccination. 3.Post-vaccination GMTs of anti-pertussis (PT, FHA, PRN, and FIM), tetanus,
diphtheria, and pneumococcal antigens..
Data analysis plan: The number of subjects enrolled and their age at enrollment (mean, median,
and minimum and maximum), sex, and ethnic origin will be summarized for each group, as well as
the number and description of protocol violations.
292
Continuous variables will be presented by summary statistics (eg, mean and standard deviation
for the non-immunogenicity endpoints, and geometric means and their confidence intervals for the
immunogenicity endpoints), and categorical variables will be presented by frequency distributions
(frequency counts, percentages, and their confidence intervals).
Progress: This protocol closed to enrollment with fifteen subjects enrolled during FY06; two
subjects in Group 1, and thirteen subjects in Group 2. Twelve subjects completed all study
interventions. Three were withdrawn prior to study completion; one left the MAMC area, one
parent requested to withdraw and one for non-compliance with study requirements. Six month
follow-up visits were completed on eleven subjects; four subjects were considered lost to follow-up
after phone contact was unsuccessful and certified letters sent. Data analysis is in progress.
293
Detail Summary Sheet
Date: 30 Sep 06 Number: 203052 Status: Completed
Title: Improving the Delivery of Influenza Vaccine to Young Children: A Comparison of Two
Influenza Vaccine Regimens
Principal Investigator: COL Mary P. Fairchok, MC
Department: Pediatrics Facility: MAMC
Associate Investigator(s): Janet A. Englund, M.D.; Kathleen M. Neuzil, M.D., M.P.H.
Start - Completion: Funding: Periodic Review:
4/21/2003 - Mar 2004 Dr. Englund (UW) via Proffer 3/22/2005
Study Objective: To compare reactogenicity and immunogenicity of two different dosing
regimens of standard licensed trivalent inactivated influenza virus vaccines (TIV) in healthy
young children ages 6-23 months.
Technical Approach: This is a prospective, randomized, open-label clinical trial comparing
reactogenicity and Immunogenicity of two different dosing regimens of standard licensed trivalent
inactivated influenza (TIV) vaccines in healthy young children ages 6-23 months. Approximately
150 patients will be enrolled her at MAMC. Patients will be randomized to either the "standard" or
the "early" dosing schedules. Both groups will receive two doses of licensed influenza vaccine (TIV)
in the fall. However the "early" group will receive an additional dose of the licensed TIV at the
time of enrollment. Antibody responses following the two doses of the vaccine in the fall (standard
group) will be compared with antibody responses following one dose of vaccine in the spring and a
second dose in the fall (early group). A diary of the injection site and systemic symptoms and signs
for 5 days following the inoculation will be maintained by the parents. A phone call will be made to
the parent beginning three days after the immunization to verify reactions and solicit adverse
experiences. Blood samples will be collected at two time points.
Progress: This protocol is closed to enrollment, with 126 subjects consented; 117 received at least
one Fluzone vaccine as part of the study procedures. Out of 117 subjects, 84 were contacted and six
month follow-up information was obtained with no adverse events reported. Following failed phone
contact attempts and return/nonresponse to certified letters, 33 subjects were lost to follow-up for
the scheduled six month follow-up. The six month follow-up data was submitted for analysis. Final
results are pending.
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Detail Summary Sheet
Date: 30 Sep 06 Number: 205137
Status: Terminated
Title: Safety and Immunogenicity of Fluzone® Influenza Virus Vaccine (2005-2006 Formulation)
Among Healthy Children 6 to 12 Weeks of Age
Principal Investigator: COL Mary P. Fairchok, MC
Department: Pediatrics
Facility: MAMC
Associate Investigator(s): Sue E. Chambers, RN
Start - Completion: Funding:
1/24/2006 - Sep 2006 Sanofi Aventis via The Geneva Foundation
Periodic Review:
N/A
Study Objective: To demonstrate the safety of Fluzone vaccine administered to 2-month-old
children
Technical Approach: This is a multicenter, double-blinded placebo controlled trial to compare
the safety and immunogenicity of Fluzone® vaccine among healthy children aged 6 to 12 weeks of
age at enrollment who are given Fluzone vaccine plus concomitant vaccines versus control children
given placebo plus concomitant vaccines. The investigational group (Group 1) will consist of up to
60 subjects enrolled at MAMC. The control group (Group 2) will consist of up to 30 children
enrolled at MAMC. Subjects will be randomized to the investigational or control group at a ratio of
2:1. All participants will be enrolled after obtaining informed consent from their parent or
guardian.
At study visit 1, Group 1 participants will receive one 0.25 mL intramuscular injection of Fluzone®
in addition to the routinely recommended concomitant vaccines of DAPTACEL, ActHIB and
Prevnar. Group 1 participants will also receive the routinely recommended Hepatitis B vaccine
and Inactivated polio vaccine at either the first study visit, the second study visit, or any time
between the 2 study visits that is at least 7 days apart from a study visit. At study visit 1, Group 2
participants will receive one .25ml intramuscular injection of saline placebo in addition to the
routinely recommended concomitant vaccines of DAPTACEL, ActHIB and Prevnar. Group 2
participants will also receive the routinely recommended Hepatitis B vaccine and Inactivated polio
vaccine at either the first study visit, the second study visit, or any time between the 2 study visits
that is at least 7 days apart from a study visit. Both groups will be provided with a diary card to
take home at this visit, recording solicirted and unsolicited local and systemic adverse effects of
the vaccines as well as daily temperatures for the 7 days after the visit.
At study visit 2, Group 1 will receive a second 0.25ml intramuscular injection of Fluzone® in
addition to Inactivated polio vaccine and/or Hepatitis B vaccine in the opposite thigh if not
previously given. Group 2 will receive a second 0.25 ml intramuscular injection of saline placebo in
addition to Inactivated polio vaccine and/or Hepatitis B vaccine in the opposite thigh if not
previously given. Interim histories and diary cards will be collected and a second diary card will
be provided.
At study visit 3, a blood sample will be collected from all subjects. Diary cards and interim history
will be obtained. All subjects will then receive the routinely recommended childhood vaccines of
DAPTACEL, ActHIB, Prevnar and Inactivated polio vaccine.
At study visit 4, a blood specimen will be collected from all subjects.
There will be a follow up contact by phone of all study participants at 6 months after visit 2 to
solicit adverse events.
Outcome variables for safety include 1. frequency and percentage of subjects who had solicited
295
injection site and systemic reactions. 2. Frequency of subjects reporting any unsolicited adverse
events and serious adverse events and the frequencies of these events. 3. Immediate reactions,
serious adverse events and adverse events in participants who withdraw due to an adverse event.
Outcome variables for immunogenicity include 1. Geometric mean of anti-HI titers (GMT)
following the second of two Fluzone vaccinations given approximately one month apart
2. Seroprotection rate: The proportion of subjects with seroprotective titer to influenza
or concomitant vaccines.
Data analysis plan: Descriptions of the populations will be presented. The number of subjects
enrolled and their age at enrollment (mean, median, and minimum and maximum), sex, and
ethnic origin will be summarized for each group, as well as the number and description of protocol
violations. Continuous variables will be presented by summary statistics (eg, mean and standard
deviation for the non-immunogenicity endpoints, and geometric means and their confidence
intervals for the immunogenicity endpoints), and categorical variables will be presented by
frequency distributions (frequency counts, percentages, and their confidence intervals).
Progress: The PI reported the protocol terminated at MAMC 1 February 2006, due to the sponsor
meeting enrollment. CRADA/SOW approval was received 25 January 2006, which was not in time
to initiate enrollment of MAMC subjects.
296
Detail Summary Sheet
Date: 30 Sep 06 Number: 205034
Status: Completed
Title: Safety and Immunogenicity of Influenza Virus Vaccine Fluzone® 2004-2005 Among
Healthy Children 2 Months vs 6 Months of Age
Principal Investigator: COL Mary P. Fairchok, MC
Department: Pediatrics
Facility: MAMC
Associate Investigator(s): Janet A. Englund, M.D.; Sue E. Chambers, RN
Start - Completion: Funding:
4/18/2005 - Jan 2006 Aventis Pasteur via University of Washington
Periodic Review:
1/24/2006
Study Objective: To determine the safety and immunogenecity of the inactivated influenza
vaccine (Fluzone) in healthy children 2 months of age compared to a control group of 6 month olds
Technical Approach: This is a multicenter, open label, double-arm. observational and
descriptive study that will provide preliminary comparative information about the safety and
immunogenicity of Fluzone® vaccine among children aged 6 to 12 weeks (the investigational
group) versus children aged 24 to 36 weeks (the control group). The study is not designed to
achieve any preset statistical power, and no hypotheses will be tested. At MAMC, we anticipate
enrolling a total of 100 patients with 50 infants enrolled in the investigational group and 50
enrolled in the control group. Study participants will receive one 0.25 mL intramuscular injection
of Fluzone® at the time of enrollment. A blood specimen will be collected at that visit, and a 7 day
diary card will be provided to record any adverse events as well as daily temperatures for the 7
days following the immnization. At visit 2, 21-35 days following enrollment, a second
intramuscular injection of 0.25 mL of Fluzone® will be given, interim history and the first diary
will be collected and another diary card provided. At Visit 3, 21-35 days after Visit 2, a second
blood specimen will be collected, interim history and the second diary card will also be collected. A
6 month followup visit will be conducted on day 210-240 following enrollment at which time an
interim history will be obtained. Outcome variables include a comparison of mean geometric titers
in each study group against the three components of the influenza vaccine pre and post
vaccination, a comparison of the seroprotection and seroconversion rates in each group against
each of the 3 components of the vaccine, and record of adverse events after each vaccine.
Data analysis: The number of subjects enrolled and their age at enrollment (mean, median, and
minimum and maximum), sex, and ethnic origin will be summarized for each group, as
well as the number and description of protocol violations. Continuous variables will be presented
by summary statistics (eg, mean and standard deviation for the non-immunogenicity endpoints,
and geometric means and their confidence intervals for the immunogenicity endpoints), and
categorical variables will be presented by frequency distributions (frequency counts, percentages,
and their confidence intervals. Additionally, the frequency and percentage of subjects who had
solicited local and systemic reactions and their 95% two-sided exact confidence intervals will be
calculated. Also, the frequency of subjects reporting medically attended unsolicited adverse events
and serious adverse events and the frequencies of these events will be calculated.
Progress: This protocol was reported completed in July 2006; final site visit has been conducted
by the study sponsor. A total of 40 patients enrolled at MAMC in FY 2005 (May-Jul); 38 received
all study treatment/procedures, two patients withdrew after Visit 1: both received 1 dose of
Fluzone and blood draw. Reason for withdraw: one patient: moved from state related to parent
deployment and one patient self withdrew after serious adverse event (fever presented at ER and
hospitalized for R/O sepsis). This adverse event was reported to the IRB and resulted in a revision
of the informed consent document.
297
Detail Summary Sheet
Date: 30 Sep 06 Number: 205139 Status: Ongoing
Title: The Impact of Human Metapneumovirus Versus other Common Respiratory Viruses in
Infants in Fulltime Daycare
Principal Investigator: COL Mary P. Fairchok, MC
Department: Pediatrics Facility: MAMC
Associate Investigator(s): Sue E. Chambers, RN; Melinda L. Behrens, MD; MAJ Loranee E.
Braun, MC; Janet Englund, MD
Start - Completion: Funding: Periodic Review:
1/25/2006 - Oct 2006 UW via The Geneva Foundation 9/26/2006
Study Objective: To determine the impact of common respiratory viruses on infants attending
fulltime daycare. Specific objectives include the comparison of duration, lost days from daycare,
complications and incidence of the viruses studied in this population.
Technical Approach: We will be performing a prospective descriptive study on the duration,
clinical characteristics, lost days from daycare, complications and incidence of the viruses studied,
with particular attention to the comparison of these characteristics of HMPV infection relative to
the other viruses studied. We will conduct rolling enrollment up to 125 subjects/month attending
at least 20 hours of daycare per week at one of the Fort Lewis Daycare Centers. Subjects enrolled
will be 6 weeks-24 months on enrollment. We will obtain baseline enrollment clinical and
demographic data and we will then follow-up with all subjects via mailers or telephone calls on a
monthly basis, as well as with notices posted at the daycare, to determine presence of development
of acute upper respiratory tract infections. If any 2 out of our 5 defined symptoms for respiratory
tract infection should develop, subjects will be given a study visit. At that visit, a standardized
health questionnaire will be completed, and a nasal swab for reverse transcriptase per for
Respiratory Syncytial Virus, Human Metapneumovirus, Parainfluenza 1,2,3 and 4, rhinovirus,
coronavirus, influenza A and B viruses, and adenovirus will be obtained. A separate clinical visit
with a health care provider will be provided if additional assessment and intervention is
necessary. Any positive pers would then undergo quantitative assay. Parents will be provided with
a diary to complete and mail back recording symptoms and duration of the illness as well as
impact on work and daycare. Parents will be called for any positive per results and given further
information about the virus identified. All subjects will be followed from the time of enrollment
until 31 October 2006 unless disenrolled. Outcome variables include the incidence of acute upper
respiratory tract infections attributable to HPMV versus the other study viruses in the population,
attack rate of each virus in the daycare per month, characteristics of the viral infections, impact
on the family in days missed from work or daycare, and duration of infection. Co-infection with
other respiratory pathogens and secondary infections will also be recorded. Method of analysis of
these variables will be conducted using descriptive statistics
Progress: This protocol remains open to enrollment, with 54 subjects enrolled during FY06. Ten
patients have been withdrawn; five for ineligibility (removed from daycare) and five moved out of
the Fort Lewis area. The remaining 44 subjects are receiving ongoing study treatment per
protocol. Presently 83 daycare visits, 48 health care provider visits, and 131 swabs have been
performed.
298
Detail Summary Sheet
Date: 30 Sep 06
Number: 206035
Status: Ongoing
Title: Military Children at Risk ■
■ Enhancing Quality of Life (mCARE) Needs Assessment
Principal Investigator: Karen L. Fitzgerald, RN, PhD
Department: Pediatrics
Facility: MAMC
Associate Investigator(s): Janice L. Hansen, PhD; Virgina F. Randall;
Jason P. Cervenka
Start - Completion:
Funding:
Periodic Review:
12/20/2005 - Dec 2006
TATRC via MIPR
N/A
Study Objective: To delineate the needs of children with life-threatening illnesses and their
families who are eligible for care in the Military Health System (MHS). To delineate the
educational needs of pediatricians (pediatric residents, general pediatricians and pediatric sub¬
specialists) that relate to providing and coordinating care for children with life threatening
illnesses and their families. To analyze the TRICARE benefit and services provided by the MHS in
relation to the needs of children with life threatening illnesses and their families. To develop
recommendations for a program to provide health care services to military children with life
threatening illnesses and their families.
Technical Approach: This is Phase II of a needs assessment of military families with children
with life-threatening illnesses, using a case study methodology. Phase II will include case studies
of the areas surrounding the Madigan AMC, Naval Medical Center, San Diego Munson AHC at Ft.
Leavenworth, KS. Altogether, there will be case studies of the National Capitol Area (NCA), areas
surrounding installations with major medical centers, and the area surrounding a small
installation with limited services available through the direct-care MHS. Data collection will
include interviews and/or focus groups with parents, interviews and focus groups with health care
providers, and collection of TRICARE data regarding case management and utilization of care.
Three existing surveys (the FACCT End-of-Life Survey, Medical Home Assessment Tools, and a
survey of the quality of life of caregivers previously developed by the investigators with parent
advisors) will provide the basis for interview and focus group questions. Needs identified will be
compared to the services available at each site and then to the services covered by the TRICARE
benefit. In collaboration with other partners in the mCARE project, needs identified by parents of
children with life-threatening illnesses and health care providers who provide care for them will be
compared to services provided by the MHS, the TRICARE benefit, and community resources. The
assessment will also describe access and barriers to access for services from these three sources.
Subsequently, the mCARE project team will propose a model of care for military children and their
families that will provide a coordinated, comprehensive, family-centered approach to care from the
time of diagnosis of a life-threatening illness through the time of bereavement of families. This
proposal also adds the following components to the needs assessment: development of an advisory
group of parents in the NCA, a collaboration with Family Medicine, adaptation to this population
of a previously-developed measure of quality of life of caregivers, technical assistance in defining
eligibility criteria, and participation in evaluation of program components piloted by other mCARE
project team members (respite care and/or care coordination).
Progress: During 2006, data was gathered from MAMC, San Diego Naval Medical Center,
Wright-Patterson Medical Center, and within the NCA. Overall 100 health care providers and 93
parents enrolled; of these participants, 28 health care providers and 35 parents were from MAMC.
Analysis of parent transcripts from the NCA has yielded a preliminary list of themes, which has
begun to identify the needs of families and the difficulties they face. Analysis of health care
provider transcripts from NCA and MAMC has yielded a separate preliminary list of themes,
which has also begun to identify the needs of health care providers themselves and those they
recognize facing the families they see.
299
Detail Summary Sheet
Date: 30 Sep 06 Number: 205065 Status: Ongoing
Title: Staphylococcus Aureus Intestinal Colonization Among Healthy Infants
Principal Investigator: LTC Dolores M. Gries, MC
Department: Pediatrics Facility: MAMC
Associate Investigator(s): Curtis J. Donskey, M.D.; CPT Tamatha F. Zemzars, MC; CPT Katy
J. Gibson, MC; Meera R. Iyer, M.D.; MAJ Steven D. Mahlen, MS; Mary L. Myers, MT; CPT Elisa
D. O’Hern, MC
Start - Completion: Funding: Periodic Review:
7/19/2005 - May 2006 DCI 4/25/2006
Study Objective: (1) To perform a prospective survey to examine the incidence and density of S.
aureus carriage among healthy infants. (2) To evaluate whether infants with increased density of
S. aureus in stool have increased frequency of environmental and skin contamination. (3) To
examine the molecular epidemiology of S. aureus isolates among healthy infants and their
mothers. (4) To determine the potential for MRSA and other nosocomial pathogens to grow in stool
of healthy infants. (5) To determine the incidence of S. aureus infection in healthy colonized
infants during the first 2 weeks of life.
Technical Approach: A 12-month prospective study will be conducted in the MAMC Newborn
Unit and Well Child Clinic. Cultures of anterior nares, skin, discarded stool, and environmental
surfaces in the room of infants will be obtained. Cultures of the anterior nares of the mother will
be obtained. Samples will be analyzed for the presence of MSSA or MRSA. Stool samples will be
evaluated for the ability of MRSA and other important nosocomial pathogens to grow in stool
specimens. Molecular typing using pulsed-field gel electrophoresis will be performed at the
Cleveland VA Medical Center to identify the potential source of the bacteria.
Progress: This protocol remains open to enrollment with thirteen patients enrolled at MAMC.
The incidence of staph colonization thus far remains at approximately 15%. No MRSA has been
found. Enrollment and follow-up remains ongoing.
300
Detail Summary Sheet
Date: 30 Sep 06 Number: 204097 Status: Terminated
Title: Effect of Immunomodulatory Diet Upon 5-Fluorouracil Induced Oral and Intestinal
Mucostitis in Golden Syrian Hamsters (Mesocricetus auratus)
Principal Investigator: CPT Wendy T. Harsha, MC
Department: Pediatrics Facility: MAMC
Associate Investigator(s): CPT Wayne J. Harsha, MC; CPT Ellina Kalandarova, MC; COL
James M. Noel, Jr., MC; ETC Robert G. Irwin, MC; CPT Patrick M. McNutt, MS; CPT Roy F.
Thomas, MC
Start - Completion: Funding: Periodic Review:
8/11/2004 - Jul 2007 Society of Military Otolaryngologists Research 8/10/2005
Grant via T.R.U.E
Study Objective: Cancer chemotherapy often causes damage to the lining of the mouth and gut,
known as mucositis. When mucositis occurs in the mouth and throat, the patients suffer from
painful ulcerations that limit their ability to talk and eat. Additionally, mucositis in the gut
predisposes patients to secondary problems such as infections, nausea, vomiting and malnutrition.
A number of growth factors and cytokines (signaling molecules of the body) have been implicated
in intestinal and oral regeneration in various animal models involving mucositis. These factors
include glutamine, transforming growth factors alpha and beta, insulin-like growth factor, and
other cytokines. It is possible to reproduce intestinal and oral mucositis in laboratory animals
with systemic injections of 5-Fluorouracil (5-FU).
Technical Approach: The aim is to address the 5-FU induced damage to the oral and
gastrointestinal tract of hamsters. The hamsters will be fed either a standard diet or a polymeric
formula containing glutamine, transforming growth beta (TGF-Beta) and short chain fatty acids
(SCFAs). Objective and semi-objective measurements of oral ulceration will be evaluated daily
and, after sacrifice, both the oral and gastointestinal mucosa will be evaluated by an objective
pathologist who is unaware of the groups from which the samples came. In addition, during the
study we will measure nutrition parameters to include daily weights, albumin levels and
bicarbonate levels.
Progress: We completed both the pilot portion of the protocol and the first phase of study
hamsters. We made some changes to the protocol based on results seen in the pilot study then
proceeded with the first phase of study hamsters. In the 42 study hamsters, the preliminary
statistics show that the study hamsters showed improved weight and food intake versus the
control animals. The GI data is still in the process of being analyzed, and the BrDU data is still
waiting to be run. The cheek pouch data has shown a trend toward improvement in the study
animals.
301
Detail Summary Sheet
Date: 30 Sep 06 Number: 206021 Status: Ongoing
Title: EKG Screening in ROTC Cadets; Is It Useful?
Principal Investigator: CPT Erik R. Johnson, MC
Department: Pediatrics Facility: MAMC
Associate Investigator(s): CPT Mark J. Devenport, MC; LTC Robert A. Puntel, MC; LTC
Telita Crosland, MC; MAJ Victoria W. Cartwright, MC; MAJ John A. Edwards, MC
Start - Completion: Funding: Periodic Review:
11/30/2005 - Jul 2006 DCI N/A
Study Objective: (1) To determine how often screening electrocardiograms (EKG's) in ROTC
cadets disclose abnormal EKG findings, (2) which specific cardiac abnormalities are discovered, (3)
what percentage of abnormal screening EKG's disclosed life-threatening or serious cardiac illness
that require further consultation and (4) what percentage of cadets are disqualified from entering
flight school due to EKG findings and/or further evaluation.
Technical Approach: This is a retrospective study designed to have no impact whatsoever on the
routine care of the ROTC candidates seen at Ft. Lewis, Washington during the Summer of 2005 as
part of Warrior Forge. Each year, approximately 500-700 cadets undergo evaluation for flight
status as an additional part of their ROTC experience (current year's estimate is around 600) and
receive screening EKGs in addition to other routine medical evaluations. Data [age, sex, height,
weight, abnormalities listed on EKG, any consultations or further evaluations made, specifically
cardiology referral (yes/no and descriptive clinical findings of referral)] will be obtained and
recorded into an Excel spreadsheet database using medical records available (CHCS, ICDB, and
Aviation Medicine Clinic medical records available for review). Results of each cadet's flight status
(yes/no) will be requested from Aviation Medicine Clinic.
Progress: Data anaylsis completed and abstract sent to USPS, but not accepted. Investigators
plan to review this past summer's RPTC EKG records to add more numbers to the data.
302
Detail Summary Sheet
Date: 30 Sep 06 Number: 203119 Status: Ongoing
Title: Alternating Antipyretics: Antipyretic Efficacy Of Acetaminophen Versus Acetaminophen
Alternated With Ibuprofen In Children
Principal Investigator: CPT Lynne C. Kramer, MC
Department: Pediatrics Facility: MAMC
Associate Investigator(s): COL Mary P. Lairchok, MC; COL (Ret) Patrick C. Kelly, D.O.; CPT
Amy M. Thompson, MC; CPT Peaches A. Richards, MC; CPT Keith R. Compton, MC; CPT David
P. Harper, MC
Start - Completion: Funding: Periodic Review:
2/27/2004 - Feb 2004 American Academy of Pediatrics via The 8/22/2006
Geneva Foundation
Study Objective: To compare the antipyretic efficacy of alternating ibuprofen and acetaminophen
to acetaminophen alone.
Technical Approach: Infants and children 6 months to 6 years meeting inclusion and exclusion
criteria who present to the pediatric clinic with a fever of 100.4 or greater will be offered
enrollment into the study. Baseline temperature will be recorded and initial dose of
acetaminophen will be given. All temperature measurements will be made using a standard oral or
rectal thermometer provided by the investigators. Parents will receive a handout and instruction
on facts and myths related to fever and fever control in children. Baseline demographic data will
be recorded to include age, sex, race, and underlying medical conditions. Parents or caregivers will
be trained to take temperature with the study thermometer and administer study medications.
Subjects will be randomized via computer based random number to either the acetaminophen
group or the acetaminophen/ ibuprofen group. Group selection will be unblinded only to the co¬
investigator entering the study medications into CHCS. Study medications will include
acetaminophen, ibuprofen, and placebos designed to mimic ibuprofen and acetaminophen. Each
patient will receive a study medication or placebo at time zero, 3 hours and 4 hours.
Acetaminophen group will receive acetaminophen time zero, placebo time 3 hours and
acetaminophen time 4 hours. Acetaminophen + ibuprofen group will receive acetaminophen time
zero, ibuprofen time 3 hours and placebo time 4 hours.
Temperatures will be obtained and recorded from each subject at 0, 3, 4, 5 and 6 hours. The study
will end at 6 hours. All subjects will receive standard of care for their presenting complaints. The
study will not interfere with the evaluation or treatment of these complaints. Once the medical
evaluation for the presenting complaint is complete subjects will be sent home or admitted
depending on their medical condition. For subjects at home, the parent or caretaker will complete
the study. A study investigator will contact the parent or caretaker at 6 hours and obtain the
results. At the conclusion of the study period, parents will read the provided instruction sheet on
what further antipyretics and antipyretic schedule may be administered to the child in the case of
continuing fever. The information will be provided as a sealed instruction sheet matched to the
randomized group, so that the study investigator will remain blinded.
Progress: This protocol is closed to enrollment with 38 subjects enrolled; eleven in the last year.
Follow-up is complete and data analysis is underway with efforts to produce a manuscript by the
end of August 2006.
303
Detail Summary Sheet
Date: 30 Sep 06 Number: 205110
Status: Ongoing
Title: AALL03N1, Understanding the Ethnic and Racial Differences in
with Acute Lymphoblastic Leukemia
Survival in Children
Principal Investigator: MAJ Kenneth H. Lieuw, MC
Department: Pediatrics
Facility: MAMC
Associate Investigator(s): COL Kelly J. Faucette, MC; MAJ Melissa A. Forouhar, MC
Start - Completion: Funding:
11/17/2005 - May 2008 COG/POG via The Geneva Foundation
Periodic Review:
7/10/2006
Study Objective: (1) To determine and compare adherence to 6-MP in a cohort of children with
ALL from four different ethnic and racial groups (Caucasians, African-Americans, Hispanics, and
Asians) receiving maintenance chemotherapy, using the following assessments: serial red cell 6-
MP metabolites (6TGN and MethylTIMP), frequency of 6-MP dosing using an electronic pill
monitoring system (MEMS®), and self-report of adherence to 6-MP by questionnaire. (2) To
determine the impact of adherence to 6-MP (measured using 6TGN, MeTIMP, MEMS® and self-
report data independently) on event-free- survival (EFS) in the entire cohort, after adjusting for
known predictors of disease outcome. (3) Define a critical level of adherence (measured
independently by 6TGN, MeTIMP, MEMS®, self-report) that has a significant impact on EFS for
the entire cohort. (4) Describe prevalence of adherence to 6-MP by ethnicity (6TGN, MeTIMP,
MEMS®, Selfreport). (5) Describe behavioral and socio-demographic predictors of adherence using
the questionnaire data. (6) Describe the pill-taking practices in this cohort using the MEMS® data.
(7) To evaluate the impact of adherence on ethnic/racial difference in EFS. (8) To assess the
concordance among 6TGN and MeTIMP levels, electronic pill monitoring, and self-reported
adherence in the ethnic/racial groups.
Technical Approach: This study will assess adherence to 6-MP in a cohort of children with ALL
from four different ethnic and racial groups (Caucasians, African-Americans, Hispanics, and
Asians), who are receiving maintenance chemotherapy, by measuring red cell 6-MP metabolites
(6TGN, MethylTIMP), frequency of 6-MP dosing using an electronic pill monitoring system
(MEMS), and self/care-giver report of adherence to 6-MP. Participants will be asked to provide 5
ml blood samples during 7 time points and complete an adherence questionnaire at 4 time points
during their regularly scheduled clinic appointments. Blood samples will be used for analysis of
genetic polymorphisms related to the efficacy of anti-leukemic therapy, and measurement of red
cell 6TGN/TIMP levels (eg. TPMT). Participants will also be given an electronic cap to use with
their 6-MP medication bottle that will record the date and time of bottle opening. The COG
anticipates about 720 patients less than or equal to 21years of age will be participating in this
study. The enrollment for MAMC is estimated to be 2-3 patients per year.
Progress: This protocol remains open to enrollment with no patients enrolled.
304
Detail Summary Sheet
Date: 30 Sep 06 Number: 206052 Status: Ongoing
Title: ACNS0331 A Study Evaluating Limited Target Volume Boost Irradiation and Reduced
Dose Craniospinal Radiotherapy (18.00 Gy) and Chemotherapy in Children with Newly
Diagnosed Standard Risk Medulloblastoma: A Phase III Double Randomized Trial
Principal Investigator: MAJ Kenneth H. Lieuw, MC
Department: Pediatrics Facility: MAMC
Associate Investigator(s): COL Kelly J. Laucette, MC; MAJ Joseph P. Brooks, MC; MAJ
Melissa A. Lorouhar, MC
Start - Completion: Funding: Periodic Review:
3/30/2006 - Oct 2009 COG/POG via The Geneva Foundation N/A
Study Objective: Primary Objective: To determine whether reducing the craniospinal dose of
radiation therapy to 18.00 Gy in children 3-7 years of age does not compromise event-free survival
and overall survival as compared to treatment with 23.40 Gy of craniospinal radiation; and to
determine if reducing the irradiated volume of the primary site tumor boost from the whole
posterior fossa to the tumor bed only will not compromise event-free and overall survival.
Secondary Objectives: To evaluate patterns of failure in children treated with an irradiation boost
volume smaller than conventional posterior fossa volumes. To reduce the cognitive, auditory and
endocrinologic effects of treatment of average-risk medulloblastoma by reducing the dose of
craniospinal irradiation therapy. To determine if the audiologic and endocrinologic toxicity will be
reduced with the use of limited tumor boost volume irradiation compared to patients treated with
conventional target volumes of radiation. To develop an optimal gene expression medulloblastoma
outcome predictor, validated prospectively in a multi-institution randomized clinical trial. To
improve compliance with long-term quality of life and functional status data submission by
educating institutional nurses to administer and submit for analysis a battery of four instruments:
Behavior Assessment System for Children (BASC), Adaptive Behavior Assessment System
(ABAS), Behavior Rating Inventory of Executive Function (Brief), PedsQLTM 4.0.
Technical Approach: In order to compare the effects of different doses and volumes of radiation,
children will be randomized to radiation treatment plans at the time of study entry. Children ages
3 and less than age 8 will be randomized twice. They will be randomized between two doses of
craniospinal radiation and between a standard volume boost and a smaller volume boost. All
children 8 years and older will be given the standard dose of craniospinal radiation and will only
be randomized for the boost volume of radiation. Chemoradiotherapy begins about 4 weeks after
surgery. Radiation therapy to the brain and spine will be given 5 days each week for 6 weeks.
Vincristine will be given IV push once a week for 6 weeks beginning at Week 1 (one week after the
start of radiation). Maintenance Chemotherapy begins 4 weeks after the completion of
chemoradiotherapy. There will be 9 cycles of maintenance; two different kinds of cycles given.
Cycle A lasts for 6 weeks and Cycle B for 4 weeks (given after the completion of 2 A cycles).
Progress: This protocol is open to patient entry, with no patients enrolled during FY06.
305
Detail Summary Sheet
Date: 30 Sep 06 Number: 206095
Status: Ongoing
Title: AEWS02B1, A Group wide Biology and Banking Study for Ewing Sarcoma
Principal Investigator: MAJ Kenneth H. Lieuw, MC
Department: Pediatrics
Facility: MAMC
Associate Investigator(s): MAJ Melissa A. Forouhar, MC
Start - Completion: Funding:
7/26/2006 - May 2016 COG/POG via The Geneva Foundation
Periodic Review:
N/A
Study Objective: Objectives: (1) To develop a mechanism to collect and distribute tumor
specimens to various investigators, and a system to prioritize and develop quality-control
measures for central data reporting of studies undertaken. (2) To determine the prognostic
significance of translocation subtype in Ewing sarcoma; to determine the prognostic significance of
translocation negative Ewing sarcoma. (3) To determine the prognostic significance of MRD
detection in bone marrow specimens by RT-PCR determination of EWS-ETS fusion genes. (3) To
determine whether serum levels of IGF1, IGFBP3 are of significance in the outcome of patients
with Ewing sarcoma. (4) To determine whether RNA expression profiles performed on diagnostic
specimens will allow for the identification of newer prognostic categories and potentially new
molecular targets for treatment in Ewing sarcoma. (5) To identify new treatment targets for
therapy. Further testing of these potential targets will be carried out in hopes of expediting
translation of these findings to the clinic. (6) To establish a bank of Ewing sarcoma xenografts in
SCID/Beige mice. (7) To establish clinical proteomics as a resource for investigations of altered
signaling molecules in the pathogenesis of Ewing sarcoma.
Technical Approach: Study AEWS02B1 is a biology and banking study for Ewing Sarcoma
designed to analyze biological factors of Ewing's tumors and relate tumor characteristics to
treatment outcomes. At initial diagnosis extra tumor specimens will be sent to the Children's
Oncology Group (paraffin blocks or unstained slides and thick sections, blood, bone marrow,
serum, fresh sterile tumor frozen in OCT media, and fresh sterile tumor in RPMI). Pathologists
are encouraged to submit additional tumor tissue obtained at the time of later biopsies or surgical
procedures to document response, recurrence, or progressive disease, and tissue obtained at
autopsy. Enrollment for MAMC is estimated to be 1-2 patients per year.
Progress: This protocol remains open to patient entry, with no patients enrolled.
306
Detail Summary Sheet
Date: 30 Sep 06 Number: 206096
Status: Ongoing
Title: AHOD0431, A Phase III Study for the Treatment of Children and Adolescents with Newly
Diagnosed Low Risk Hodgkin Disease
Principal Investigator: MAJ Kenneth H. Lieuw, MC
Department: Pediatrics
Facility: MAMC
Associate Investigator(s): MAJ Melissa A. Forouhar, MC
Start - Completion: Funding:
8/11/2006 - Feb 2009 COG/POG via The Geneva Foundation
Periodic Review:
N/A
Study Objective: Objectives: (1) To investigate the paradigm of response-based therapy for low
risk Hodgkin disease by eliminating involved-field radiation therapy (IFRT) for subjects who
achieve a CR with initial chemotherapy. (2) To investigate whether three cycles of AV-PC* for the
treatment of low risk Hodgkin disease is sufficient to induce CR in at least 80% of subjects. (3) To
investigate whether subjects who experience a low risk relapse after initial treatment with
chemotherapy alone can be successfully treated with a salvage regimen consisting of IV/DECA and
IFRT. (3) To maintain the overall survival (OS) for subjects with low risk Hodgkin disease at or
above 97%. (4) To determine the prognostic significance of very early response as measured by
FDG-PET or gallium after the first course of chemotherapy. (5) To evaluate the prognostic
significance of elevation of ESR and CRP at the time of diagnosis in low risk Hodgkin disease on
CR rate and relapse rate after chemotherapy alone. (6) To determine the frequency and severity of
late effects of therapy including thyroid dysfunction, infertility, cardiotoxicity and second
malignant neoplasms.
Technical Approach: All patients will have initial treatment utilizing AV-PC* with or without
involved field radiation therapy. Those patients who are in complete remission after three cycles of
AV-PC* will begin follow-up. Those patients who are in partial remission after three cycles will
receive involved field radiation therapy. Those who fail to achieve a partial remission with initial
chemotherapy, who have progressive disease prior to completing initial therapy, or who fail to
achieve a complete remission after radiation therapy will be off study. All patients with a positive
FDG-PET (or gallium) prior to initiating treatment will have a second scan after one course of AV-
PC* utilizing the same modality as the initial scan (FDG-PET strongly encouraged if available).
Those with a persistently positive study will have a third scan after chemotherapy to document
remission status. Patients who experience a biopsy proven low risk recurrence after achieving a
complete remission with chemotherapy alone will be treated with a salvage regimen. The initial
treatment will consist of 3 cycles of AV-PC*. Each cycle is 21 days in duration and commences on
Day 1 if the ANC > 750 (with patients off G-CSF for at least 2 days) and platelets are > 75,000.
Subjects in complete remission after three courses of initial chemotherapy will stop treatment and
begin follow-up. Subjects with partial remission after three courses of initial chemotherapy will
proceed to involved field radiation therapy. Radiation therapy will commence approximately 4
weeks after the 3rd cycle of AV-PC* is completed and when ANC >1000 and platelet count
>100,000. Patients who experience a biopsy proven low risk relapse after achieving a complete
remission with chemotherapy alone at initial treatment, and therefore have not had prior
radiation therapy, will be treated with two cycles of Ifosfamide and Vinorelbine, followed by two
cycles of Dexamethasone, Etoposide, Cisplatin, ARA-C followed by involved field radiation therapy.
Each cycle will be 21 days in length. All relapses must be biopsy proven. All patients on the
salvage regimen will proceed to involved field radiation therapy after four cycles of salvage
chemotherapy. Radiation therapy will commence approximately 4 weeks after the 2nd cycle of
DECA is completed and when ANC >1000 and platelet count >100,000.
Progress: This protocol remains open to patient entry, with no patients enrolled.
307
Detail Summary Sheet
Date: 30 Sep 06 Number: 206051
Status: Ongoing
Title: ANBL0032 Phase III Randomized Study Of Chimeric Antibody 14.18 (Chl4.18) In High
Risk Neuroblastoma Following Myeloablative Therapy And Autologous Stem Cell Rescue
Principal Investigator: MAJ Kenneth H. Lieuw, MC
Department: Pediatrics
Facility: MAMC
Associate Investigator(s): MAJ Melissa A. Forouhar, MC
Start - Completion: Funding:
4/6/2006 - Oct 2006 COG/POG via The Geneva Foundation
Periodic Review:
N/A
Study Objective: Primary objective to determine if monoclonal antibody Chl4.18 + cytokines +
isotretinoin (13-cis-retinoic acid, or RA) improves event free survival after myeloablative therapy
and stem cell rescue as compared to RA alone, in high risk neuroblastoma patients who have
achieved a pre-ASCT response of CR, VGPR, or PR.
Secondary objectives: (1) to determine if monoclonal antibody Chl4.18 + cytokines + isotretinoin
(13-cis-retinoic acid, or RA) improves overall survival after myeloablative therapy and stem cell
rescue as compared to RA alone, in high risk neuroblastoma patients who have achieved a pre-
ASCT response of CR, VGPR, or PR. (2) Determine if immunotherapy + RA improve event free
survival and overall survival as compared to RA alone, in the subgroup of high risk INSS stage 4
neuroblastoma patients who have achieved a pre-ASCT response of CR, VGPR, or PR. (3) To
determine the variability of 13-cis-retinoic-acid pharmacokinetics and relationship to
pharmacogenomic parameters and determine if these levels and/or genetic variations correlate
with EFS or systemic toxicity. (4) In the subgroup of neuroblastoma patients who have achieved a
pre-ASCT response of CR, VGPR, or PR, determine if there is a difference between the two
randomized regimens in reducing the minimal residual disease (MRD) burden as detected by the
following parameters: meta-iodobenylguanidine (MIBG) scan, immunocytology (IC) of blood and
bone marrow samples, RT-PCR for tyrosine hydroxylase, PGP 9.5, and MAGE-1 in blood and bone
marrow. (5) Determine if change from baseline of MRD as measured by above parameters is
associated with event free and overall survival. (6) Determine whether tumor biology at diagnosis
correlates with event-free and overall survival, for either of the randomized regimens. (7)
Determine the toxicities of the combination of monoclonal Chl4.18 with cytokines. (8) To explore
the relationship between antibody-dependent cellular cytotoxicity (ADCC) and EFS. (9) To
determine a descriptive profile of human anti-chimeric antibody (HACA) during immunotherapy.
(10) To compare the outcome data of the patients with persistent disease documented by biopsy
(stratum 07) to the historical data for the analogous patients from CCG-3981.
Technical Approach: Patients will be enrolled and randomized into regimen A or B on day 50
post-ASCT, up to day 77 (see special exemption) post-ASCT when 1) total absolute phagocyte count
(APC) is at least 1000/?L 2) organ functions have met the eligibility criteria, and, 3) tumor
assessment has been completed following the end of radiotherapy at least 5 days before.
Randomization will be stratified by pre-ASCT CR versus VGPR versus PR and by purging vs.
nonpurging of the stem cells for ASCT. Regimen A consists of oral intake of isotretinoin (13-cis-
retinoic acid, or RA) starting day 66 post-ASCT at 80 mg/m2/dose twice a day for 14 days every 28
days, for 6 courses. For regimen B, patients will receive oral isotretinoin (13-cis-retinoic acid, or
RA) as in regimen A. In addition, patients will receive 5 courses of chl4.18 + cytokines, with
chl4.18 + GM-CSF administered in courses 1, 3, and 5, and chl4.18 + aldesleukin (IL-2) given in
courses 2 and 4. The intervals between antibody administrations are 28 days for all courses.
Progress: This protocol is open to patient entry, with no patients enrolled during FY06.
308
Detail Summary Sheet
Date: 30 Sep 06 Number: 206097
Status: Ongoing
Title: AREN03B2; Renal Tumors Classification, Biology, and Banking Study
Principal Investigator: MAJ Kenneth H. Lieuw, MC
Department: Pediatrics
Facility: MAMC
Associate Investigator(s): MAJ Melissa A. Forouhar, MC
Start - Completion: Funding:
7/26/2006 - Indef COG/POG via The Geneva Foundation
Periodic Review:
N/A
Study Objective: To classify patients with renal tumors by histological categorization, surgical-
pathological stage, presence of metastases, age at diagnosis, tumor weight and loss of
heterozygosity for chromosomes lp and 16q, to thereby define eligibility for a series of therapeutic
studies. To maintain a biological samples bank to make specimens available to scientists to
evaluate additional potential biological prognostic variables and for the conduct of other research
by scientists.
Technical Approach: This classification protocol will provide the mechanism to identify renal
tumor patients on a population basis, and to describe their characteristics at diagnosis. This study
will also establish the natural history (relapse-free and overall survival) for patients with disease
for which there will not be a therapeutic or outcomes study (all renal tumors except Wilms,
rhabdoid, clear cell sarcoma, and renal cell carcinoma). These cases, after central review results
are reported back to the enrolling Institution, will be followed (date of last follow-up, relapse, and
death) as part of their enrollment on AREN03B2. It is expected that all such patients, even with
benign tumor, will be followed at least yearly, for a period of about ten years, by the enrolling
Institution (at the time of enrollment, institutions will be notified which cases must be followed).
Patients less than 30 years of age will be participating in this study. The enrollment for MAMC is
estimated to be 1-2 patients per year.
Progress: This protocol is open to patient entry, with one patient enrolled at MAMC during FY06.
309
Detail Summary Sheet
Date: 30 Sep 06 Number: 200032
Status: Completed
Title: COG 9900, ALinC 17, Classification (C), B-Precursor Induction Treatment (I) Protocol
Principal Investigator: MAJ Kenneth H. Lieuw, MC
Department: Pediatrics
Facility: MAMC
Associate Investigator(s): COL Kelly J. Faucette, MC
Start - Completion: Funding:
1/25/2000 - Jan 2005 COG/POG via The Geneva Foundation
Periodic Review:
12/8/2005
Study Objective: (1) To provide the clinical and laboratory data necessary for placing each
patient with ALL onto proper therapeutic trial, and (2) to provide an administrative base to
capture classification data for correlative studies in ALL treatment protocols and series of
historical protocols.
Technical Approach: At the time of diagnostic evaluation which includes bone marrow
aspiration and/or biopsy, 20 ml of bone marrow and 25 ml of peripheral blood will be collected and
processed for local laboratory studies and submission to the following POG reference laboratories:
1. Johns Hopkins University for Immunophenotyping. 2. University of New Mexico (UNM) for
DNA Index, FISH, Molecular testing, Cell banking. 3. Medical College of Wisconsin for
Glucocorticoid receptors. 4. University of Texas Southwestern Medical Center for Homocysteine
Children's Hospital of Michigan for Drug sensitivity profiles. 5. MUSC - Children's Hospital for
Drug sensitivity profiles. UCSD Medical Center for Tumor suppressor gene studies. The data
captured on this protocol will be used in the therapeutic trials, in cross era analysis, and in
international collaborations to further define the prognostic importance of biologic features in
ALL.
Progress: This protocol was reported as completed in August 2006, with eleven patients enrolled
at MAMC, none during FY06. One patient is deceased and the other ten patients will continue to
be followed under their therapeutic protocols.
310
Detail Summary Sheet
Date: 30 Sep 06 Number: 200077
Status: Ongoing
Title: COG 9904, ALinC 17: Treatment for Patients with Low Risk Acute Lymphoblastic
Leukemia, A Phase III Study
Principal Investigator: MAJ Kenneth H. Lieuw, MC
Department: Pediatrics
Facility: MAMC
Associate Investigator(s): COL Kelly J. Faucette, MC
Start - Completion: Funding:
5/12/2000 - May 2004 COG/POG via The Geneva Foundation
Periodic Review:
4/25/2006
Study Objective: (1) In conjunction with POG 9905, to compare short MTX infusion (2g/m2 over 4
hours) with a longer infusion (lg/m2 over 24 hours), primarily with respect to efficacy and
secondarily with respect to toxicity. (2) to determine in a randomized trial, if a delayed multi- drug
intensification, administered in the context of intensive anti-metabolite therapy, will improve
outcome for children with ALL, (3) To determine the correlation between peripheral blood and CSF
concentrations of homocysteine and its metabolites and acute (seizures) and chronic neurotoxicity
(neurocognitive dysfunction), and (4) To determine the relationship between a membrane bound
glucocorticoid receptor and EFS via quantitation of the glucocorticoid receptor concentrations in
marrow samples at diagnosis.
Technical Approach: This protocol will randomize between the 4-hour and 24 hour methotrexate
infusion and for patients with TEL/AML1 gene, between standard and delayed intensification.
Data from POG 9904 and 9905 will be pooled for statistical analysis of efficacy and toxicity. This
study will determine the correlation between peripheral blood and CSF concentrations of
homocysteine and its metabolites and acute (seizures) and chronic neurotoxicity (neurocognitive
dysfunction). Induction will include three or four drugs (dependent on initial risk classification
POG 9900).
Progress: This protocol closed to patient entry in April 2005, with four patients enrolled. One
patient remains on treatment and three patients have completed study treatment; all continued to
be followed at MAMC during FY06.
311
Detail Summary Sheet
Date: 30 Sep 06 Number: 200139 Status: Ongoing
Title: COG A5971: Randomized Phase III Study for the Treatment of Newly Diagnosed
Disseminated Lymphoblastic Lymphoma or Localized Lymphoblastic Lymphoma, A Phase III
COG Study
Principal Investigator: MAJ Kenneth H. Lieuw, MC
Department: Pediatrics
Facility: MAMC
Associate Investigator(s): COL Kelly J. Faucette, MC; MAJ Melissa A. Forouhar, MC
Start - Completion: Funding:
9/26/2000 - Sep 2007 COG/POG via The Geneva Foundation
Periodic Review:
8/24/2006
Study Objective: (1) To compare the event free survival and survival in patients with
disseminated lymphoblastic lymphoma treated on four regimens. (NHL/BFM-95 vs. CCG BFM), (2)
To determine if treatment with a regimen without high dose methotrexate will maintain the same
excellent disease free survival obtained with NHL/BFM-90, (3) To determine if intensification
with anthracycline and cyclophosphamide improves disease free survival, (4) To collect outcome
data on uniformly treated patients with localized disease or CNS positive disease, and (5) To
determine if rapid reduction in tumor volume as defined by chest radiography and CT is predictive
of improved outcome.
Technical Approach: Patients with disseminated (Murphy stage III or IV) lymphoblastic
lymphoma without evidence of CNS disease will be randomized to one of four treatment regimens:
Standard CCG BFM (regimen Al); CCG BFM intensified with cyclophosphamide/anthracycline
intensification during the induction and delayed intensification phases (regimen A2); Standard
NHL/BFM-95 (regimen BI); or NHL/BFM-95 intensified with cyclophosphamide/anthracycline
intensification during the induction and delayed intensification phases (regimen B2). Patients with
disseminated lymphoblastic lymphoma positive for CNS disease will be assigned to the intensified
NHL/BFM-95 arm (regimen B2) with delayed radiation therapy. Patients with localized
lymphoblastic lymphoma (Murphy stage I or II) will be assigned to the standard CCG BFM arm
without additional intrathecal methotrexate (regimen AO). The duration of each treatment arm is
2 years and consists of Induction, Consolidation, Interim Maintenance, Delayed Intensification,
and Maintenance therapies.
Progress: COG temporarily closed accrual to this protocol in September 2005, to assess whether
the number of evaluable patients was sufficient to answer the study question. Madigan had
enrolled one patient in 2004, who is currently being treated at WRAMC, although MAMC
continues to be responsible for data submission to COG. COG lifted the temporary suspension and
the protocol was approved by the IRB to continue patient enrollment at MAMC on 26 September
2006.
312
Detail Summary Sheet
Date: 30 Sep 06 Number: 205015
Status: Ongoing
Title: COG AALL0031, A COG Pilot Study for the Treatment of Very High Risk Acute
Lymphoblastic Leukemia in Children and Adolescents
Principal Investigator: MAJ Kenneth H. Lieuw, MC
Department: Pediatrics
Facility: MAMC
Associate Investigator(s): COL Kelly J. Faucette, MC
Start - Completion: Funding:
4/5/2005 - Jun 2005 COG/POG via The Geneva Foundation
Periodic Review:
10/24/2006
Study Objective: Primary Objective: To determine the feasibility in terms of patient accrual and
toxicity of an intensified chemotherapeutic regimen incorporating novel agents for treatment of
children and adolescents with very high risk (VHR) ALL. Secondary Objectives: (1) To determine if
the BCR-ABL-specific tyrosine kinase inhibitor STI571 can be incorporated into this regimen with
acceptable toxicity for patients with Ph+ ALL. (2) To compare EFS for VHR patients treated with
the intensive chemotherapy with that of historical controls. (3) To conduct a preliminary
evaluation of the feasibility and efficacy of following intensive consolidation by Hematopoietic
Stem Cell Transplantation (HSCT) as therapy for patients with HLA matched related donors. (4)
To determine if MRD assessed at the end of induction and prior to reinductioin and prior to HSCT
therapy by PCR and flow cytometry can predict elapse. (5) To evaluate whether MRD detected by
PCR at post-intensification time points is prognostically significant. (6) To evaluate whether gene
expression patterns can be identified by microarray evaluations to predict disease recurrence or
response to STI571.
Technical Approach: This pilot study will utilize a novel intensified chemotherapeutic regimen
for VHR patients based on (1) the use of ifosfamide and etoposide in POG ALL relapse studies; (2)
the use of high dose methotrexate for children and infants; and (3) the intensive CCG New York II
regimen used for patients with lymphomatous ALL. The study will determine whether an
adequate number of VHR patients will be accrued to form the basis for development of a future
phase III trial within the COG. The presence or absence of minimal residual disease in patients in
remission also will be determined. If the intensive treatment is found to have acceptable toxicity
and shows potential, either alone, or with transplant, for improving outcome of the VHR patient
population, it will be the first promising strategy identified for this group. The accrual goal is 110
patients over a 2 year time frame.
Progress: This protocol closed to accrual in October 2006. MAMC enrolled one patient enrolled
who continued to be followed during FY06. The patient is no longer receiving study treatment.
313
Detail Summary Sheet
Date: 30 Sep 06 Number: 205068 Status: Ongoing
Title: COG AALL0232, High Risk B-precursor Acute Lymphoblastic Leukemia
Principal Investigator: MAJ Kenneth H. Lieuw, MC
Department: Pediatrics Facility: MAMC
Associate Investigator(s): COL Kelly J. Faucette, MC; MAJ Melissa A. Forouhar, MC
Start - Completion: Funding: Periodic Review:
7/29/2005 - Mar 2015 COG/POG via The Geneva Foundation 5/23/2006
Study Objective: (1) To improve the outcome of children with high risk acute lymphoblastic
leukemia. (2) To determine the relative safety and efficacy of dexamethasone given for 14 days
versus prednisone given for 28 days during Induction. (3) To determine the relative safety and
efficacy of high dose methotrexate (5gm/m2) with Leucovorin rescue compared to escalating
methotrexate without Leucovorin rescue (Capizzi I) delivered during Interim Maintenance. (4) To
correlate Day 29 Minimal Residual Disease (MRD) with Event Free Survival (EFS) and Overall
Survival (OS). (5) To correlate early marrow response status with Day 29 MRD status. (6) To
improve outcome by identifying additional high risk patients by day 29 MRD for treatment with
fully augmented BFM.
Technical Approach: This study will compare the use of two steroid drugs, dexamethasone and
prednisone, during induction and will examine the best way to give methotrexate during the
interim maintenance phase of treatment. This study will use a known chemotherapy regimen that
has been very effective for treating children with high risk ALL and test whether two changes to
this treatment can cure more patients without increasing side effects. The aim of the first change
is to test whether 14 days of dexamethasone is tolerated without an increased number of severe
side effects and is better than 28 days of prednisone in decreasing the number of leukemia cells
during the first month of treatment. The aim of the second change is to determine whether giving
higher doses of methotrexate, during interim maintenance, will work better than giving it on a
schedule that starts with a lower dose and increases with each of the later doses.
Progress: This protocol remains open to enrollment with two patients enrolled at MAMC, 1
during FY06. Two patients received study treatment. One patient was an induction failure, was
taken off study and enrolled onto another COG protocol.
314
Detail Summary Sheet
Date: 30 Sep 06 Number: 205095 Status: Ongoing
Title: COG AALL0331, Standard Risk B-precursor Acute Lymphoblastic Leukemia; A Phase III
Group-Wide Study
Principal Investigator: MAJ Kenneth H. Lieuw, MC
Department: Pediatrics Facility: MAMC
Associate Investigator(s): COL Kelly J. Faucette, MC; MAJ Melissa A. Forouhar, MC
Start - Completion: Funding: Periodic Review:
12/15/2005 - July 2009 COG/POG via The Geneva Foundation 6/27/2006
Study Objective: (1) To determine whether the substitution of three intensified phases of post¬
induction treatment for standard phases will improve the event free survival (EFS) of children
with SR-average acute lymphoblastic leukemia (ALL). (2) To determine whether the addition of
four doses of PEG Asparaginase, given once every three weeks during consolidation and interim
maintenance phases, will improve the EFS for children with SR-low ALL. (3) To identify
potentially modifiable factors associated with impaired health related quality of life (HRQOL) at
different periods of therapy in the patients who are SR-average enrolled on the standard risk ALL
study. (4) To determine the critical time periods when future intervention studies to mitigate
adverse HRQOL outcomes should occur. (5) To correlate Day 29 Minimal Residual Disease (MRD)
with EFS and Overall Survival (OS). (6) To correlate early marrow response status with Day 29
MRD status. (7) To improve outcome by identifying additional high risk patients by Day 29 MRD
for treatment with fully augmented BFM. (8) To examine the relative contributions of genetic
factors and early treatment response to outcome by comparing the outcome of patients with and
without TEL-AML1 fusion or triple trisomy and low levels of MRD at end Induction who are
treated with identical therapy on the standard arms of the SR-low and SR-average trials.
Technical Approach: Patients treated on this study will receive multiple drugs all designed to
kill leukemia cells. Patients who have an appropriate donor will be given a blood and marrow
transplant. Those without an appropriate donor will continue on with more chemotherapy.
Patients with high levels of cancer cells in the spinal fluid will also receive radiation to the brain.
Boys with leukemia cells in the testes will receive radiation to the testes. Patients receiving a
blood and marrow transplant will also be given radiation to the entire body before their transplant
and will be hospitalized for about three months during treatment. The new drug for patients with
leukemia containing the Philadelphia chromosome positive (Ph+) is called Imatinib (STI571), and
it is given throughout treatment. If a patient goes on to have a blood and marrow transplant,
Imatinib (STI571) may be given after the transplant at the transplant center or at the primary
care center
Progress: This protocol remains open to enrollment with one patient enrolled during FY06 and
continuing to receive treatment.
315
Detail Summary Sheet
Date: 30 Sep 06 Number: 205067 Status: Ongoing
Title: COG AALL03B1, Classification of Acute Lymphoblastic Leukemia
Principal Investigator: MAJ Kenneth H. Lieuw, MC
Department: Pediatrics Facility: MAMC
Associate Investigator(s): COL Kelly J. Faucette, MC; MAJ Melissa A. Forouhar, MC
Start - Completion: Funding: Periodic Review:
7/11/2005 - Mar 2015 COG/POG via The Geneva Foundation 4/25/2006
Study Objective: To provide a classification guide that will organize the clinical and laboratory
data necessary for assigning each patient with newly diagnosed ALL to a specific therapeutic trial.
(2) To provide an administrative base to capture classification data for correlative studies
accompanying current Children's Oncology Group (COG) ALL treatment protocols. (3) To provide a
central reference guide for all required and research only studies that will be conducted at local
and reference laboratories for all newly diagnosed patients with ALL. (4) To provide a mechanism
for optional banking of leukemia and germ line specimens for current and future research.
Technical Approach: This COG risk group classification protocol will serve as a foundation for
patients with newly diagnosed ALL. Registration on this protocol will be a requirement for entry
onto any COG therapeutic study. The purpose of this classification protocol for ALL is to integrate
data from recently completed clinical trials into an organized framework to appropriately risk
stratify and treat patients enrolled in COG clinical trials for ALL. Patients will be assigned to an
induction treatment regimen on the basis of studies that are performed at the host institution.
Additional samples will also be sent by the local institution to one or more COG ALL reference
labs at the time of diagnosis and at defined time points during therapy. This data will be used to
refine subsequent therapy at the end of induction by assignment to a specific treatment protocol
for defined risk groups in non-infant B-precursor ALL and/or via non-randomized allocation to
specific treatment regimens within a given trial. The classification study will also be used for
participation in companion biology research studies that are not used for treatment allocation and
for voluntary banking of leukemia cells for future research. Approximately 8000 people will take
part in this study across the United States and abroad. Madigan Army Medical Center plans to
enroll 2-3 patients per year.
Progress: This protocol remains open to enrollment with three patients enrolled at MAMC, 2
during FY06. All three patients have been enrolled in treatment studies and are currently
receiving treatment.
316
Detail Summary Sheet
Date: 30 Sep 06 Number: 205026 Status: Completed
Title: COG AAML03P1, Treatment of Newly Diagnosed Childhood Acute Myeloid Leukemia
(AML) Using Intensive MRC-Based Therapy and Gemtuzumab Ozogamicin (GMTZ): A COG
Pilot Study
Principal Investigator: MAJ Kenneth H. Lieuw, MC
Department: Pediatrics
Facility: MAMC
Associate Investigator(s): COL Kelly J. Faucette, MC
Start - Completion:
3/16/2005 - Jan 2006
Funding:
COG/POG via The Geneva Foundation
Periodic Review:
N/A
Study Objective: To determine the safety of adding a single dose of gemtuzumab ozogamicin
(GMTZ) to a well established intensive two-course MRC-based regimen (Medical Research Council)
for remission Induction of children with newly diagnosed AML. (2) To determine the complete
remission rate of a remission Induction regimen that consists of two consecutive courses of
cytarabine, daunorubicin, and etoposide (ADE) plus a single dose of GMTZ in the initial course of
ADE. (3) To determine the safety of adding a single dose of GMTZ to one course of post-remission
Intensification therapy for children with newly diagnosed AML. (4) To determine the feasibility of
performing biological studies (FLT3-ITD, MRD) for risk group stratification. (5) Feasibility
component with the following objective: To determine the proportion of AML patients with primary
induction failure (PIF) for whom a suitable unrelated stem cell donor can be made available within
21 days of study entry, and, identify obstacles to rapid donor identification..
Technical Approach: This study combines GMTZ with standard chemotherapy and consists of
four phases. Patients with <20% blasts at the end of phase I (Induction I) receive phase II ADE.
Patients in complete remission at the end of phase II (Induction II) proceed to phase III AE
(Intensification #1). Patients with matched family donors who complete Intensification #1 and who
remain in remission will be assigned to receive allogeneic BMT. Patients without matched family
donors who complete Intensification #1 and who remain in remission will be assigned
chemotherapy (MA+GMTZ followed by Capizzi II). This study will stop accruing when 150 patients
have been evaluated. This accrual goal should be met in less than a year.
Progress: COG reported accrual goals reached as of 1 November 2005; no subjects enrolled at
MAMC.
317
Detail Summary Sheet
Date: 30 Sep 06 Number: 205122
Status: Completed
Title: COG ACNS0126, A Phase II Study of Temozolomide in the Treatment of Children with
High-grade Glioma or diffuse intrinsic Pontine Gliomas
Principal Investigator: MAJ Kenneth H. Lieuw, MC
Department: Pediatrics
Facility: MAMC
Associate Investigator(s): COL Kelly J. Faucette, MC
Start - Completion: Funding:
8/22/2005 - Oct 2006 COG/POG via The Geneva Foundation
Periodic Review:
7/18/2006
Study Objective: (1) To determine whether temozolomide given during radiation therapy and as
adjuvant therapy results in an improvement in event-free survival compared to historical control
cohorts. Target tumors are: Anaplastic Astrocytoma, Glioblastoma Multiforme, Gliosarcoma and
Diffuse Intrinsic Pontine Gliomas. (2) To further assess the toxicity of temozolomide in a larger
group of patients treated during XRT and during adjuvant treatment. (3) To evaluate the efficacy
of temozolomide in the treatment of children with diffuse intrinsic Pontine gliomas. (4) To monitor
the toxicity of this therapy in the treatment of children with diffuse intrinsic pontine gliomas.
Laboratory Correlates (HGG Patients Only): (1) Investigate MGMT expression in formalin-fixed,
paraffin-embedded biopsy specimens of brain tumors using immunohistochemical methods. (2)
Identify those tumors in which MGMT expression is silenced by determining promoter CpG
methylation in DNA isolated from formalin-fixed, paraffin-embedded tumor samples. (3)
Investigate whether a functional MMR system is present in tumor cells by using microsatellite
instability assays to compare DNA isolated from formalin-fixed paraffin-embedded tumor samples
with DNA isolated from the patient's peripheral blood white cells. (4) Determine p53 expression
using standardized immunohistochemical techniques. p53 mutation analysis will incorporate
microdissection-based topographic genotyping and direct sequence analysis. (5) Determine MIB-1
indices in tumor samples using standardized immunohistochemical techniques.
Technical Approach: Temozolomide will be given concurrently with radiation therapy to newly
diagnosed children with High Grade Glioma (HGG) or Diffuse Intrinsic Pontine Gliomas (DIPG)
on a 42-day schedule. Four weeks following the completion of radiation therapy the patient will
receive temozolomide daily for 5 days beginning a new cycle every 28 days for a total of 10 cycles.
COG anticipates about 50 patients between the ages of 3 and 22 years of age will be participating
in this study; enrollment at MAMC is estimated to be 1 to 2 patients per year.
Progress: This protocol closed to enrollment in July 2006. One MAMC subject enrolled but died of
disease progression.
318
Detail Summary Sheet
Date: 30 Sep 06 Number: 206034 Status: Ongoing
Title: COG ACNS0423: A Phase II Study of Concurrent Radiation and Temozolomide Followed
by Temozolomide and Lomustine (CCNU) in the Treatment of Children with High Grade Glioma
Principal Investigator: MAJ Kenneth H. Lieuw, MC
Department: Pediatrics Facility: MAMC
Associate Investigator(s): COL Kelly J. Faucette, MC; LTC John B. Halligan, MC; MAJ
Melissa A. Forouhar, MC
Start - Completion: Funding: Periodic Review:
12/21/2005 - Mar 2006 COG/POG via The Geneva Foundation 11/30/2006
Study Objective: (1) To determine whether temozolomide given during radiation therapy
followed by the combination of Temozolomide and CCNU as adjuvant therapy results in an
improvement in event-free survival compared to historical control cohorts. Target tumors are: o
Anaplastic Astrocytoma; Glioblastoma Multiforme; Gliosarcoma. (2) To further assess the toxicity
of adjuvant treatment with CCNU and temozolomide following XRT and concurrent temozolomide
in a larger group of patients.
Laboratory Correlates: (1) Investigate MGMT expression in formalin-fixed, paraffin-embedded
biopsy specimens of brain tumors using immunohistochemical methods. (2) Identify those tumors
in which MGMT expression is silenced by determining promoter CpG methylation in DNA isolated
from formalin-fixed, paraffin-embedded tumor samples. (3) Investigate whether a functional MMR
system is present in tumor cells by using micro satellite instability assays to compare DNA isolated
from formalin-fixed paraffin-embedded tumor samples with DNA isolated from the patient's
peripheral blood white cells. (4) Determine p53 expression using standardized
immunohistochemical techniques. p53 mutation analysis will incorporate microdissection-based
topographic genotyping and direct sequence analysis. (5) Determine MIB-1 indices in tumor
samples using standardized immunohistochemical techniques. (6) Determine the frequencies of
GSTM1, GSTT1, and GSTP1 allelic variants in patients with high grade glioma. (7) Determine the
level of protein expression of GSTP1 in tumor specimens. (8) Determine whether polymorphisms in
GSTP1, GSTM1 and GSTT1 genes and tumor GSTP1 protein expression are associated with
survival, hypothesizing that patients with inherent low activity GST genotypes and low GSTP1
protein expression will have increased survival time. (9) Assess whether germline polymorphisms
of the GST genes are correlated with severity of chemotherapy toxicity, hypothesizing that
patients with low activity GST genotypes will have decreased clearance of the metabolites of
chemotherapy agents, and thus will have higher degree of toxicity. (10) Characterize allelic
imbalance and copy number changes associated with high-grade gliomas by Affymetrix SNP
arrays. (11) Characterize gene expression changes associated with high-grade gliomas by
Affymetrix U133plus2 arrays. (12) To correlate any identified chromosomal abnormalities and
differentially expressed genes with clinical parameters such as age, tumor location, degree of
resection, histological grade, p53 expression, progression free survival, overall survival, treatment
responses to determine their prognostic significance. (13) Identify oncogenes and tumor suppressor
genes involved in the pathogenesis and malignant phenotype of pediatric high grade gliomas.
Technical Approach: Patients will be given radiation therapy (RT) to the brain 5 days a week for
6 weeks. Within the first week of starting RT the patient will begin taking Temozolomide orally
(90 mg/m2/day) and continue taking the drug for 42 days (6 weeks). After completion of RT and the
6-week treatment with Temozolomide, patients will be given no treatment for a 4-week rest period.
During Maintenance, patients will take oral Temozolomide again, but this time at a higher dose
(160 mg/m2/day) for five days in a row followed by a 37 day break. In addition, patients will take
another chemotherapy drug known as Lomustine (CCNU) orally with the temozolomide on day 1.
319
Patients will be treated on this study for about 11-12 months. Expected enrollment for MAMC is 1-
2 patients per year.
Progress: This protocol remains open to patient entry, no patients have enrolled.
320
Detail Summary Sheet
Date: 30 Sep 06 Number: 205084
Status: Ongoing
Title: COG AGCT0132, A Phase III Study of Reduced Therapy in the Treatment of Children
with Low and Intermediate Risk Extracranial Germ Cell Tumors
Principal Investigator: MAJ Kenneth H. Lieuw, MC
Department: Pediatrics
Facility: MAMC
Associate Investigator(s): COL Kelly J. Faucette, MC; MAJ Melissa A. Forouhar, MC
Start - Completion: Funding:
11/25/2005 - Nov 2009 COG/POG via The Geneva Foundation
Periodic Review:
5/22/2006
Study Objective: Low Risk (LR) (1) To assess whether the proposed therapeutic plan can
maintain a 3-year survival of at least 95% for patients newly diagnosed with Stage I gonadal
malignant germ cell tumors. (2) To determine the cytogenetic and molecular genetic features
which correlate with clinical differences in behavior. These tissues will be banked for future
analyses of the biologic characteristics of malignant germ cell tumors.
Intermediate Risk (IR) (1) To assess whether three cycles of 3-day compressed PEB chemotherapy
can maintain a 3-year event-free survival of at least 92% for patients with newly diagnosed Stage
II-IV malignant testicular and Stage II-III ovarian germ cell tumors, newly diagnosed Stage I-II
non-gonadal extracranial malignant germ cell tumors, or relapsed/progressed immature
teratomas. (2) To determine the cytogenetic and molecular genetic features which correlate with
clinical differences in behavior. These tissues will be banked for future analyses of the biologic
characteristics of malignant germ cell tumors. (3) To assess whether three cycles of 3-day
compressed PEB chemotherapy can maintain a 3-year survival of at least 95% for patients with
newly diagnosed Stage II-IV malignant testicular and Stage II-III ovarian germ cell tumors, newly
diagnosed Stage I-II non-gonadal extracranial malignant germ cell tumors, or relapsed/progressed
immature teratomas with malignant components.
Cancer Control Objectives (1) To estimate the percentage of patients with Stage I ovarian and
Stage I testicular GCTs for whom chemotherapy can be eliminated in the first three years
following diagnosis. (2) To estimate the percentage of intermediate risk patients requiring only
three cycles of therapy. (3) To delineate the acute toxicities and long term sequelae associated with
therapy compression. These will be compared with historical data available from CCG-8882/POG-
9049. (4) To determine the number of hospital days and total drug dosages required for the
compressed therapy. These will be compared with historical data available from CCG-8882/POG-
9049. (5) To compare the number of protocol directed treatment days of CCG-8882 with the
number of treatment days used in AGCT0132.
Tumor Biology Objectives (1) To collect samples and facilitate studies of germ cell tumor
cytogenetics and molecular genetics including deletion, mutation and imprinting on chromosomes
1 and 6, and amplification of c-myc. (2) To derive tumor cell lines and xenografts of germ cell
tumors for use in studies of biologic agents and
differentiation agents. (3) To establish a biologic samples bank for germ cell tumors to include
frozen tumor and frozen normal tissue that may be used in future studies.
Technical Approach: AGCT0132 is a Phase III Study of Reduced Therapy in the Treatment of
Children with Low and Intermediate Risk Extracranial Germ Cell Tumors. This study would avoid
chemotherapy in low risk testicular/ovarian germ cell tumors by using surgery and observation. If
during observation the tumor markers do not return to normal or become abnormal, the patient
will be treated with chemotherapy in 3 cycles over a period of 9 weeks. Each treatment will involve
3 anti-cancer drugs: cisplatin, etoposide, and bleomycin. In patients with intermediate risk the
321
standard therapy would be surgery plus chemotherapy. The purpose of this study would be to
decrease the total amount of chemotherapy given from 4 cycles to 3. The number of days
chemotherapy would be given would also decrease from 5 to 3 days in each treatment cycle.
Progress: This protocol remains open to enrollment, with no patients enrolled.
322
Detail Summary Sheet
Date: 30 Sep 06 Number: 203024 Status: Ongoing
Title: COG AHOD0031, A Phase III Group-wide Study of Dose-intensive Response-based
Chemotherapy and Radiation Therapy for Children and Adolescents with Newly Diagnosed
Intermediate Risk Hodgkin Disease
Principal Investigator: MAJ Kenneth H. Lieuw, MC
Department: Pediatrics
Facility: MAMC
Associate Investigator(s): COL Kelly J. Faucette, MC; MAJ Melissa A. Forouhar, MC
Start - Completion:
1/13/2003 - Mar 2008
Funding: Periodic Review:
COG/POG via The Geneva Foundation 12/12/2006
Study Objective: (1) To compare response-based therapy to standard therapy for intermediate
risk Hodgkin disease. (2) To determine whether involved field radiation therapy (IFRT) can be
eliminated based upon early and complete response to multiagent chemotherapy. (3) To determine
whether the addition of an additional two cycles of chemotherapy (DECA) can improve outcome in
those with a slow early response to standard chemotherapy. (4) To prospectively collect
information on the individual prognostic significance of the following presenting factors:
erythrocyte sedimentation rate, circulating levels of IL-100, each of the "B" symptoms - fever,
night sweats, weight loss, nodal aggregate > 6cm, large mediastinal mass> 1/3 thoracic diameter
and number of involved nodal sites, histology, albumin, blood counts, sex and age. (5) To study the
reliability and utility of [18F] - Fluorodeoxyglucose (FDG) Imaging (PET scans) as an imaging
modality in Hodgkin disease. (6) To determine the frequency and severity of late effects of therapy
including thyroid dysfunction, infertility, cardiotoxicity, pulmonary toxicity and second malignant
neoplasms. (7) To serve as the therapeutic companion to biology and late effects studies in
Hodgkin disease and correlate those results with response to therapy, event free- survival and
overall survival.
Technical Approach: All patients will receive 3 cycles of ABVE-PC three weeks apart followed
by a re-evaluation of disease. Those with a rapid early response will receive an additional 1 cycle of
ABVE-PC three weeks later followed by another re-evaluation of disease. Rapid early responders,
who have sustained a complete response following a total of 4 cycles of ABVE-PC chemotherapy,
will be randomized to omit (reduced therapy arm) or receive consolidative low dose involved field
radiation therapy (IFRT) (standard therapy arm). Those with less than a complete response will
receive IFRT. Patients with a slow early response to 3 cycles of ABVE-PC will be randomized to
receive 1 additional cycle of ABVE-PC (standard therapy arm) alone versus 1 additional cycle of
ABVE-PC preceded by 2 cycles of DECA (augmented therapy arm) . All patients who are slow
early responders will receive consolidative low dose IFRT. Patients with less than a complete
response after consolidative radiation therapy or those with progressive disease at any time will be
treated at the discretion of the treating physician after consultation with the study chair.
Progress: This protocol remains open to patient entry with two patients enrolled, none during
FY06. One patient had recurrent disease and enrolled in another COG protocol. The other patient
continued to be followed at MAMC.
323
Detail Summary Sheet
Date: 30 Sep 06 Number: 205047
Status: Completed
Title: COG AHOD00P1, A Pilot Study of Re-Induction Chemotherapy with Ifosfamide, and
Vinorelbine (IV) in Children with Refractory/Relapsed Hodgkin Disease
Principal Investigator: MAJ Kenneth H. Lieuw, MC
Department: Pediatrics
Facility: MAMC
Associate Investigator(s): COL Kelly J. Faucette, MC
Start - Completion: Funding:
5/31/2005 - Jan 2006 COG/POG via The Geneva Foundation
Periodic Review:
1/24/2006
Study Objective: (1) To determine the response rate of the re-induction regimen
ifosfamide/vinorelbine (IV) with filgrastim overall and within the cohorts of minimally pre¬
treated/low risk and heavily pre-treated/high risk patients with relapsed/refractory Hodgkin
disease. (2) To evaluate ifosfamide/vinorelbine (IV) with filgrastim as a re-induction regimen in
minimally pretreated/low risk pediatric patients with relapsed/refractory Hodgkin disease.
Specifically, to determine: (a) the cardiac, hepatic, renal, and hematologic toxicity, and toxic death
rate and (b) the proportion of patients able to mobilize sufficient hematopoietic stem cells (CD34+)
after 2 cycles of IV. To collect data regarding tumor biologic characteristics in patients with
relapsed/refractory Hodgkin disease (a) To determine the incidence of hyper mutability in Hodgkin
patients by longitudinal genotoxic bio-monitoring and (b) To determine the prognostic significance
of biologic markers including serum IL-10 receptor, serum IL-2 receptor, p53, and mdm-2.
Technical Approach: This is a phase II pilot study of re-induction chemotherapy with Ifosfamide
and Vinorelbine (IV) in children with refractory/relapsed Hodgkin disease. Subjects will have two
cycles of chemotherapy, Ifosfamide and Vinorelbine, at least 21 days apart. Filgrastim will be
given on day 6 of each cycle, or anytime tests show the white blood cell count is too low, to help
white-blood cells grow. Subjects will be evaluated at the end of cycle 2. Subject's whose disease
worsens will be taken off study therapy. Subject's whose disease remains the same will have a
stem cell collection and then be taken off study therapy. Subject's whose disease responds to
treatment will have a stem cell collection at the end of cycle two. Stem cell transplantation will not
be performed at MAMC; subjects will be referred to a COG approved bone marrow transplant
center.
Progress: COG closed enrollment in March 2006, with no subjects enrolled at MAMC.
324
Detail Summary Sheet
Date: 30 Sep 06 Number: 205014
Status: Ongoing
Title: COG AHOD0321, A Phase II Study of Weekly Gemcitabine and Vinorelbine in Children
with Recurrent or Refractory Hodgkin Disease
Principal Investigator: MAJ Kenneth H. Lieuw, MC
Department: Pediatrics
Facility: MAMC
Associate Investigator(s): COL Kelly J. Faucette, MC; MAJ Melissa A. Forouhar, MC
Start - Completion: Funding:
12/6/2004 - Dec 2005 COG/POG via The Geneva Foundation
Periodic Review:
10/24/2006
Study Objective: To determine the response rate after weekly administration of the combination
of gemcitabine and vinorelbine to patients with recurrent or refractory Hodgkin Disease. To
document the toxicity of weekly administration of gemcitabine and vinorelbine in patients with
recurrent or refractory Hodgkin Disease.
Technical Approach: This is a Phase II study of weekly Gemcitabine and Vinorelbine In children
with recurrent or refractory Hodgkin Disease. This study will evaluate the use of a new re¬
induction chemotherapy regimen consisting of the anti-cancer drugs combination of gemcitabine
and vinorelbine in patients who have previously been treated for Hodgkin Disease. Patients will
receive at least two cycles (21 days each) of weekly GEM/VINO therapy. The goal is to determine if
the combination of these is active against recurrent Hodgkin Disease and to find out what effects
this drug combination will have. Patients with any response after the first two cycles may elect to
proceed directly to stem cell transplantation. Those with stable disease after the first two cycles,
will receive a minimum of two more cycles of GEM/VINO. At the end of the fourth cycle, patients
without progressive disease can remain on study and continue to receive GEM/VINO or go off
study for alternative therapy. About 26 patients between the ages of 0 to <30 years of age will be
participating in this study.
Progress: This protocol remains open to enrollment with one patient enrolled who is off study
treatment but continued to be followed at MAMC after having gone through bone marrow
transplant.
325
Detail Summary Sheet
Date: 30 Sep 06 Number: 201108 Status: Ongoing
Title: COG ANBL00B1, Neuroblastoma Biology Studies
Principal Investigator: MAJ Kenneth H. Lieuw, MC
Department: Pediatrics Facility: MAMC
Associate Investigator(s): COL Kelly J. Faucette, MC; MAJ Melissa A. Forouhar, MC
Start - Completion: Funding: Periodic Review:
6/26/2001 - May 2007 COG/POG via The Geneva Foundation 5/23/2006
Study Objective: (1) To prospectively analyze the factors that are currently used for risk-group
assignment (DNA content by flow cytometry, MYCN copy number by FISH, and tumor histology
using the International Neuroblastoma Pathologic Classification System) in neuroblastoma
tumors at the time of diagnosis, (2) to maintain a reference bank containing clinically and
genetically characterized frozen tumor tissue, tumor DNA and RNA, tumor touch preparations,
histology slides and blocks, cell lines, and paired normal DNA obtained at the time of diagnosis (all
patients), at the time of second-look surgery (high-risk patients), and relapse (all patients) for
future research studies, (3) to prospectively analyze the prevalence of lp, llq, 14q LOH and gain
of 17q; the expression of nerve growth factor (NGF) and its high affinity (Trk-A) and low affinity
(p75 NTR) receptors; and telomerase activity in diagnostic neuroblastoma tumors, and to
determine the independent clinical significance of these biologic factors compared to MYCN
amplification, INSS stage, age, and histologic variables in predicting either response to treatment
or outcome, (4) to build a database of the known biologic prognostic factors for patients on
therapeutic studies, (5) to serve as a Registry for neuroblastoma patients whose tumors
demonstrate clinical and genetic features defined as "Low Risk" for treatment failure in the
absence of adjuvant therapy, and (6) A secondary objective of this study is to prospectively analyze
the role of ferritin, LDH, and Imaging-defined risk factors identified at the time of diagnosis in
risk assessment.
Technical Approach: Clinical and biological factors have been shown to have prognostic value in
neuroblastoma. Current therapeutic studies for neuroblastoma patients are tailored according to
patient risk. In the Children's Oncology Group (COG), risk-group assignment is currently based on
INSS stage, age, MYCN copy number, tumor cell ploidy, and Shimada tumor histopathology.
However, additional factors have also been shown to have prognostic value including the level of
Trk-A expression, multi-drug resistance associated protein (MRP) expression, telomerase activity,
CD44 expression, and genetic abnormalities including LOH of lp, llq, 14q and gain of 17q. We
hypothesize that analyzing additional genetic and biologic factors will result in a further
refinement of the current COG risk-group schema, and will, thereby, impact future risk-based
approaches to therapy. We further hypothesize that maintaining tumor and nucleic acid banks
with well characterized samples will provide invaluable biologic resources for future research
studies that will lead to a further understanding of neuroblastoma biology and the development of
new, effective therapy for high-risk patients.
Progress: This study remains open to patient entry, with three patients enrolled at MAMC, two
during FY06. One patient was transferred to Seattle Children's Hospital in July 2006. Data on the
two remaining patients continued to be submitted to COG.
326
Detail Summary Sheet
Date: 30 Sep 06 Number: 205069 Status: Completed
Title: COG ANHL0121, A Phase II Study of Rituximab (IND#7028) and Ifosfamide, Carboplatin
and Etoposide (ICE) Chemotherapy in Children with Recurrent/Refractory B-cell (CD20+) Non-
Hodgkin Lymphoma and B-cell Acute Lymphoblastic Leukemia
Principal Investigator: MAJ Kenneth H. Lieuw, MC
Department: Pediatrics
Facility: MAMC
Associate Investigator(s): COL Kelly J. Faucette, MC
Start - Completion:
7/6/2005 - Nov 2007
Funding:
COG/POG via The Geneva Foundation
Periodic Review:
4/20/2006
Study Objective: Primary Aims: (1) To determine the response and relapse-free survival rates to
chemotherapy with ifosfamide, Carboplatin, and etoposide plus rituximab for patients with
recurrent/refractory CD 20+ NHL and B-cell ALL. (2) To evaluate the toxicity profile of this
therapy regimen. Specifically, the frequency of therapy delays between courses due to prolonged
Grade 4 hematologic toxicity will be monitored. Secondary Aims: (1) To determine whether
ifosfamide, Carboplatin, and etoposide in combination with rituximab and G-CSF will result in
mobilization of greater than 2 x 106/kg peripheral blood stem cells (CD34+ cells, PBSC) in at least
80% of patients for whom peripheral stem cell collection is performed. (2) To evaluate the time
course of engraftment for patients who undergo peripheral stem cell transplantation following
collection of stem cells using this mobilization regimen. (3) To collect tumor specimens to permit an
evaluation of gene expression profiles in patients with recurrent/refractory CD20+ NHL and B-cell
ALL. (4) To collect tumor and other specimens to permit the identification of patient- specific
markers for use in evaluation of presence and significance of minimal residual disease.
Technical Approach: This study will address adding an investigational drug, Rituximab, to
standard chemotherapy called ICE (ifosfamide, Carboplatin, and etoposide) in an attempt to
improve the outcome of patients who have not responded well to standard treatment alone.
Patients will be on this study for up to three months, depending on how the disease is responding
to treatment. Patients who have disease which gets worse after one course of chemotherapy will
not continue on the study drugs. Patients who have disease that stays the same or responds at all
to treatment will receive a second course of therapy. There will be a third course of therapy for
patients who show a continued response. Some patients may have peripheral blood stem cells
collected during therapy which would be stored and used later in case patients need more
treatment.
Progress: This protocol closed to accrual on 23 Oct 2006, with no MAMC subjects enrolled.
327
Detail Summary Sheet
Date: 30 Sep 06 Number: 200049 Status: Ongoing
Title: COG D9902, A COG Soft Tissue Sarcoma Diagnosis, Biology and Banking Protocol
Principal Investigator: MAJ Kenneth H. Lieuw, MC
Department: Pediatrics Facility: MAMC
Associate Investigator(s): COL Kelly J. Faucette, MC; MAJ Melissa A. Forouhar, MC
Start - Completion: Funding: Periodic Review:
2/22/2000 - Feb 2010 COG/POG via The Geneva Foundation 1/19/2006
Study Objective: (1) To facilitate the collection of human tissue and other biologic specimens
(blood, bone marrow) from Intergroup Rhabdomyosarcoma Study Group (IRSG) investigators, (2)
To provide a repository for long-term storage of tissue and other biologic specimens (blood, bone
marrow) collected by IRSG investigators (referred to as the Bank), and (3) To make available,
through the IRSG/Cooperative Human Tissue Network, these materials for approved projects by
laboratory-based investigators.
Technical Approach: At the time of initial diagnosis of rhabdomyosarcoma or undifferentiated
sarcoma (or at re-excision of the primary tumor, if it occurs prior to the start of chemotherapy),
surgical tissue, bone marrow and blood that are no longer needed for diagnosis will be prepared
and shipped to the Pediatric Cooperative Human Tissue Network (CHTN) for Banking and
Distribution.
Progress: This protocol is open to patient entry with two patients enrolled at MAMC, none during
FY06. Both patients have moved out of the MAMC area. Follow up data is not required under this
tissue banking protocol.
328
Detail Summary Sheet
Date: 30 Sep 06 Number: 98090 Status: Ongoing
Title: COG P9442: National Wilms Tumor Late Effects Study
Principal Investigator: MAJ Kenneth H. Lieuw, MC
Department: Pediatrics Facility: MAMC
Associate Investigator(s): COL Kelly J. Faucette, MC
Start - Completion: Funding: Periodic Review:
7/17/1998 - Indef COG/POG via The Geneva Foundation 6/20/2006
Study Objective: To determine (1) the frequency of Wilms tumor and other cancers in family
members of Wilms tumor patients in order to estimate the recurrence risk in siblings and
offspring; test the plausibility of specific genetic modes of inheritance in homogeneous subgroups;
and identify familial cancer syndromes (if any) that may involve Wilms tumor, (2) To determine
fertility rates of Wilms tumor patients and rates of perinatal mortality, low birth-weight and
adverse pregnancy outcomes in relation to the type and amount of cancer treatment received in
childhood, (3) To estimate the rates of selected congenital defects and of specified single gene
disorders (sentinel phenotypes) in the offspring of Wilms tumor patients, (4) to estimate the rates
of second malignancy neoplasms in relation to the dosage of radiation therapy and the use of
specific chemotherapeutic agents (Actinomycin D, doxorubicin, Cytoxan and etoposide) received in
childhood, (5) to compare the incidence rate of congestive heart failure among Wilms tumor
survivors in relation to the dose of radiation therapy received to abdomen and/or lungs and to the
use of specific chemotherapeutic agents.
Technical Approach: The large number of Wilms tumor survivors ascertained by the NWTS
during its first twenty years of operation constitutes an ideal cohort for the study of familial risk
and late effects of treatment. Four protocol studies have been conducted; treatment protocols and
results for the first three studies have been published. A large fraction of the total national U.S.
incidence of Wilms tumor has been registered on these studies, probably as much as 70% of an
estimated 450-500 cases occurring nationally since 1980. Over 2,500 children who were followed on
NWTS treatment protocols have now survived 5 or more years since their original diagnosis. Many
of those treated more than a decade ago have reached sexual maturity, so that their reproductive
history and the status of their offspring may be evaluated by entry into this study.
Progress: This protocol remains open to enrollment with no subjects enrolled to date at MAMC.
329
Detail Summary Sheet
Date: 30 Sep 06 Number: 201054 Status: Completed
Title: COG P9934: Systemic Chemotherapy, Second Look Surgery and Conformal Radiation
Therapy Limited to the Posterior Fossa and Primary Site for Children > 8 Months and < 3 Years
with Non-metastatic Medulloblastoma - A Children's Oncology Group Phase III Study
Principal Investigator: MAJ Kenneth H. Lieuw, MC
Department: Pediatrics Facility: MAMC
Associate Investigator(s): COL Kelly J. Faucette, MC; COL John D. Werschkul, MC; COL
Marc G. Cote, MC; LTC William B. Reece, MC
Start - Completion: Funding: Periodic Review:
1/23/2001 - Jan 2006 COG/POG via The Geneva Foundation 1/4/2006
Study Objective: (1) To determine if the proposed treatment for children > 8.0 months and < 3
years of age at registration with non-metastatic (M0) medulloblastoma is more effective than the
combined treatments given to children of the same age and extent of disease on POG 9233, as
measured by event-free survival (EFS) rates, (2) to assess the feasibility and safety of the planned
use of second look surgery and focal conformal radiation therapy following chemotherapy, (3) to
determine the acute and chronic toxicities associated with the above treatment regimens, (4) to
describe the neuropsychological and neuroendocrine effects of this systemic chemotherapy,
surgery, and local, conformal radiation, (5) to determine the feasibility and validity of a centralized
telephone interview based data collection method for neuropsychological evaluations, and (6) to
determine the incidence of atypical teratoid/rhabdoid tumor (AT/RT) in children enrolled on this
study.
Technical Approach: In this study for young children with relatively low risk medulloblastoma,
we will test a new therapeutic approach which begins with maximal safe tumor resection and a 16-
week, 4-drug induction chemotherapy regimen of cyclophosphamide, vincristine, cisplatin, and oral
etoposide. In comparison to the chemotherapy regimens of studies 8633 and 9233, cisplatin is
introduced earlier, and given concurrently with the other agents. As well, etoposide is given in an
oral form. Based upon the compelling data that outcome is clearly linked to a complete surgical
resection the proposed therapy includes a 'second look' surgery following induction chemotherapy
in an attempt to resect residual disease in those patients who have failed to achieve a complete
response to chemotherapy. To improve local control rates this clinical trial will test the use of
conformal radiation therapy and will determine if these techniques can reduce radiation-related
side effects. Following recovery from the initial phase of treatment, patients will receive a
maintenance phase of chemotherapy, using cyclophosphamide, vincristine, and the prolonged
administration of oral etoposide, to complete one year of therapy.
Progress: This protocol closed enrollment in June 2006, with no subjects enrolled at MAMC.
330
Detail Summary Sheet
Date: 30 Sep 06 Number: 205105 Status: Ongoing
Title: COG-LTF, A Groupwide Process for Collecting Long Term Follow Up Data
Principal Investigator: MAJ Kenneth H. Lieuw, MC
Department: Pediatrics Facility: MAMC
Associate Investigator(s): COL Kelly J. Faucette, MC; MAJ Melissa A. Forouhar, MC
Start - Completion: Funding: Periodic Review:
7/12/2005 - indef COG/POG via The Geneva Foundation 6/20/2006
Study Objective: The specific objective is to establish a single mechanism for regular annual
local Institutional Review Board (IRB) approval for COG member institutions by aggregating
protocols for which only follow-up data collection is needed.
Technical Approach: This document is designed to facilitate follow-up data collection for
Children's Oncology Group (COG) studies that are closed to accrual and for which all patients in
an institution have completed therapy. This includes studies that originated in the Children's
Cancer Group (CCG), the Pediatric Oncology Group (POG), the Intergroup Rhabdomyosarcoma
Study Group (IRSG), and the National Wilms Tumor Study Group (NWTSG) as well as new COG
studies.
Progress: This protocol remains ongoing with 31 patients now being followed under this long¬
term administrative protocol. No patients were entered during. Twenty nine continued to be
followed; two are not lost to follow up.
331
Detail Summary Sheet
Date: 30 Sep 06 Number: 94092 Status: Ongoing
Title: POG 9351/CCG 7921: Trial of Doxorubicin, Cisplatin, and Methotrexate With and Without
Ifosfamide, With and Without Muramyl Tripeptide Phosphatidyl Ethanolamine (MTP-PE) for
Treatment of Osteogenic Sarcoma
Principal Investigator: MAJ Kenneth H. Lieuw, MC
Department: Pediatrics
Facility: MAMC
Associate Investigator(s): COL Kelly J. Faucette, MC
Start - Completion:
4/21/1995 - Indef
Funding:
COG/POG via The Geneva Foundation
Periodic Review:
3/21/2006
Study Objective: (1) To improve the survival of patients with osteogenic sarcoma, (2) To compare
the results of a prospective, randomized trial of two chemotherapeutic regimens in the treatment
of osteogenic sarcoma, (3) To compare the results of a combined chemotherapeutic regimen (high-
dost methotrexate, cisplatin, and doxorubicin) given pre-operatively and post-operatively to a
similar regimen using the same drugs and adding ifosfamide, (4) To test whether the early
introduction of ifosfamide results in a higher rate of good histologic response at the time of
definitive surgery, (5) To determine whether histologic response assessed after longer pre¬
operative chemotherapy with more drugs predicts disease-free survival with the same power as
observed in CCG-782 which used a shorter period of pre-operative chemotherapy and fewer drugs,
(6) To determine whether liposomal muramyl tripeptide-phosphatidyl ethanolamine (MTP-PE,
CGP 19835a), a stimulator of macrophage function, can improve disease-free survival for patients
with osteogenic sarcoma, (7) To determine whether multiple drug resistance gene-encoded P-
glycoprotein expression is useful for determine prognosis or assigning therapy.
Technical Approach: This study is a phase III, prospective, randomized trial of two
chemotherapy regimens for the treatment of newly diagnosed, previously untreated osteogenic
sarcoma. One regimen calls for the administration of high-dose methotrexate, doxorubicin, and
cisplatin. The other regimen calls for the administration of these agents plus ifosfamide.
Chemotherapy is administered for 10 weeks prior to surgical resection of the primary tumor and
any metastatic disease (CCG patients). Patients also are randomly assigned either to receive
muramyl tripeptide (MTP-PE) with maintenance chemotherapy or to receive maintenance
chemotherapy alone.
Progress: This protocol closed to patient entry November 1997, with two patients enrolled. One
patient chose to discontinue treatment and the other patient completed study therapy. Long-term
follow-up data continues to be submitted annually to COG on both patients.
A final report on this protocol was submitted by the study chair, Paul Meyers, M.D., 26 October
2004. Summary of recommendations and future plans: Regimen A, which calls for cisplatin,
doxorubicin, and high dose methotrexate, achieved EFS at least as good as regimen B, which calls
for the same three agents with the addition of ifosfamide. Regimen A had less toxicity than
regimen B. Until an appropriate prospective randomized trial is available, regimen A should be
considered standard therapy for osteosarcoma. The interaction between MTP and ifosfamide needs
further study. In vitro analysis of the interaction should be encouraged and clinical trials
considered of the combination in patients at the time of recurrence.
332
Detail Summary Sheet
Date: 30 Sep 06 Number: 95058 Status: Completed
Title: POG 9400: ALinC 16 Classification (C) Protocol
Principal Investigator: MAJ Kenneth H. Lieuw, MC
Department: Pediatrics Facility: MAMC
Associate Investigator(s): COL Kelly J. Faucette, MC
Start - Completion: Funding: Periodic Review:
12/16/1994 - Indef COG/POG via The Geneva Foundation 11/15/2005
Study Objective: (1) To continue to characterize the biologic findings of the acute lymphoblastic
and undifferentiated leukemias (immunologic markers, ploidy (DNA index), karyotyping,
morphology) and their relationship, as prognostic factors for attaining and maintaining remission,
(2) To apply to therapy selection, the determination that ploidy and certain structural
chromosomal abnormalities predict poor prognosis, (3) To evaluate the usefulness of PCR
technique in detecting minimal residual disease in patients with disease demonstrating t ( 9; 2 2 )
or t ( 1; 19 ) chromosomal abnormalities, (optional), (4) To apply to therapy selection molecular
testing for llq23 translocation in infants < 12 months of age with acute lymphocytic leukemia, (5)
To determine the roll of p53 and pl6 tumor suppressor genes in T-ALL. (optional), (6) Individual
patient outcome will be compared with the leukemia cell proliferation response to ask if
proliferation in response to a myeloid growth factor is associated with an increased risk of
developing AML. (optional), (7) To determine risk group assessment using Fluorescent In-Situ
Hybridization (FISH) screening for Trisomies 4 and 10 in Non-T, Non B ALL, and (8) To determine
if drug sensitivity profiles of blast cells for three commonly used chemotherapeutic agents -
Adriamycin, Methotrexate, and Cytarabine correlate with a) initial response b) subsequent
development of relapse.
Technical Approach: A bone marrow aspirate (a needle stick in hip bone to draw marrow into
syringe) will be done to prove or disprove diagnosis of leukemia. If leukemia is present, it is
important to identity the exact type and subtype of leukemia, in order to plan treatment. This
typing requires that several laboratory tests be run on the leukemia cells in the bone marrow. As
we perform the bone marrow aspiration we will be removing enough bone marrow (about 2-1/2
teaspoons) to run the laboratory tests. We may also need to draw some blood (about 2-1/2
teaspoons) from a vein to send for studies. Some of these tests will be done here and some will be
sent to reference laboratories in other Pediatric Oncology Group institutions for different kinds of
special tests to identify the characteristics of the leukemia cells.
Progress: This protocol closed to patient entry in November 1999, with nine patients enrolled.
One patient has been reported lost to follow up, one patient transferred to another COG
institution, one patient relapsed, and six patients continue to be followed. COG reported the
protocol completed 31 March 2000, with a final accrual of 4211 (842 per year). Hard copy of the
final report has been placed in the protocol file.
333
Detail Summary Sheet
Date: 30 Sep 06 Number: 96097
Status: Ongoing
Title: POG 9440: National Wilms Tumor Study - 5: Therapeutic Trial and Biology Study
Principal Investigator: MAJ Kenneth H. Lieuw, MC
Department: Pediatrics
Facility: MAMC
Associate Investigator(s): COL Kelly J. Faucette, MC
Start - Completion: Funding:
4/19/1996 - Indef COG/POG via The Geneva Foundation
Periodic Review:
3/21/2006
Study Objective: (1) To increase the survival rate of children with favorable histology Wilms
tumor and other renal tumors of childhood, (2) to determine if loss of heterozygosity for
chromosome 16q markers in tumor tissue is associated with a poorer prognosis for children with
favorable histology Wilms tumor, (3) to determine if loss of heterozygosity for chromosome lp
markers in tumor tissue is associated with a poorer prognosis for children with favorable histology
Wilms tumor, (4) to determine if increased DNA content in tumor cells is associated with a poorer
prognosis, (5) to decrease the acute and long term morbidity of treatment of children with Wilms
tumor, (6) to improve the survival of patients with unfavorable histology tumors including Wilms
tumor with diffuse anaplasia and clear cell sarcoma of the kidney by using a new treatment
regimen that includes etoposide and cyclophosphamide, (7) to improve survival of patients with
malignant rhabdoid tumor of the kidney, (8) to study biology and pathology of patients who
present with bilateral Wilms tumor, (9) to conduct hypothesis-driven trials led by diagnostic
radiologists in order to develop guidelines, and (10) to establish a biological samples bank
containing touch preparations, paraffin blocks, frozen tumor, normal kidney tissue, and serum and
urine.
Technical Approach: This proposed therapeutic trial involves a number of experimental
regimens that are designed either to reduce treatment for the subgroup of patients with the most
favorable prognosis, or to intensify treatment for several subgroups with the least favorable
prognosis. Patients will be stratified into the appropriate treatment regimens by age, size of tumor
at diagnosis and staging of the tumor (Stages 1-V) with favorable/unfavorable histology, including
rhabdoid, clear cell sarcomas and Wilms tumor with diffuse or focal anaplasia. Treatment will
include nephrectomy or surgical debulking of tumor, radiation therapy to abdomen and/or lungs,
and appropriate chemotherapy regimens.
Progress: This protocol closed to patient entry in June 2002, with two patients enrolled who
continued to be followed at MAMC during FY06.
334
Detail Summary Sheet
Date: 30 Sep 06 Number: 200018
Status: Completed
Title: POG P9761: Phase II Trial of Irinotecan in Children with Refractory Solid Tumors: A
COG Study
Principal Investigator: MAJ Kenneth H. Lieuw, MC
Department: Pediatrics
Facility: MAMC
Associate Investigator(s): COL Kelly J. Faucette, MC
Start - Completion: Funding:
11/19/1999 - Nov 2004 COG/POG via The Geneva Foundation
Periodic Review:
10/14/2005
Study Objective: (1) To determine the efficacy of Irinotecan in the treatment of children with
refractory neuroblastoma, sarcomas of soft tissue or bone, other solid tumors, or brain tumors, (2)
to further evaluate the toxicity of Irinotecan when given daily for 5 days, repeated every 21 days,
and (3) to further evaluate the pharmacokinetics/pharmacodynamics of Irinotecan and its
metabolites SN-38, SN 38G, and APC, using a limited sampling strategy.
Technical Approach: Irinotecan appears to be one of the most active topoisomerase I inhibitors
that is clinically available and therefore deserves further evaluation in children with recurrent
CNS or solid tumors. Although the optimal schedule for Irinotecan is not yet known, antitumor
activity has been observed on all schedules of administration. Pharmacokinetic studies, an integral
component of this trial will be done to determine if there are correlates with PK parameters and
toxicity or response.
Progress: This protocol reached its accrual goals and was reported completed in November 2005.
One patient had been enrolled at MAMC during FY00, but died due to progressive disease.
335
Detail Summary Sheet
Date: 30 Sep 06 Number: 200048
Status: Ongoing
Title: POG P9851: Osteosarcoma Biology Protocol, Companion to Group-Wide Therapeutic
Studies
Principal Investigator: MAJ Kenneth H. Lieuw, MC
Department: Pediatrics
Facility: MAMC
Associate Investigator(s): COL Kelly J. Faucette, MC
Start - Completion: Funding:
2/22/2000 - Feb 2010 COG/POG via The Geneva Foundation
Periodic Review:
1/18/2006
Study Objective: (1) To increase our understanding of the basic biology of these tumors, with a
distinct possibility that new therapeutic targets may be uncovered. Examples of this type are
ErbB-2 and methotrexate resistance factors, (2) To develop a set of biologic prognostic indicators
which can be measured at diagnosis and which will be predictive of response and outcome in
osteosarcoma. These could then be used in subsequent treatment programs to determine therapy,
avoiding excessive toxicity to good risk patients and reserving alternative, more intensive therapy
for those at standard risk. Examples include loss of heterozygosity at Rb and MDR, (3) To
determine the feasibility of various assays and to develop a reliable mechanism of distributing
osteosarcoma samples to various intergroup investigators, with centralized reporting of laboratory
results and adequate quality control.
Technical Approach: At the time of biopsy or surgery (definitive or recurrence), tumor tissue
that is not needed for diagnosis will be processed and forwarded to the Cooperative Human Tissue
Network (CHTN) for distribution. Specimens will include: tumor tissue (Formalin-fixed or
formalin-fixed paraffin embedded block or 30 unstained slides; blood samples (heparinized (10 ml),
serum (14 ml)). Assays being performed: MDR Immunohistochemistry (University of Rochester);
MDR Functional Assays/MRP (Memorial Sloan-Kettering); Methotrexate Transport & Metab
(Memorial Sloan-Kettering) ;Topoisomerase II (Yale University); Bcl-2/Bax (Yale University);
Rb/p53 (Fels Institute); ErbB-2 (Memorial Sloan-Kettering); MDM2 (Memorial Sloan-Kettering);
pl6/p21 (Hospital for Sick Children); LOH at 3q,18q (Fels Institute); sis,gli,fos (Yale University);
SV40 (University of Colorado); myc,RAS (Memorial Sloan-Kettering); metalloproteinase (Yale
University); c-met/HGF (Yale University); IGF-I/IGF-IR (University of Maryland); Telomerase (St.
Jude Children's); Ploidy (Dana Farber).
Progress: In July 2006, COG reported that this companion protocol would be phased out and
expected to close accrual within six months after the new protocol is up and running. One patient
was enrolled at MAMC and continues to be followed, pending close-out of this protocol by COG.
336
Detail Summary Sheet
Date: 30 Sep 06 Number: 203105
Status: Completed
Title: POG P9962 A Phase II Study of Intrathecal Topotecan in Patients with Refractory
Meningeal Malignancies
Principal Investigator: MAJ Kenneth H. Lieuw, MC
Department: Pediatrics
Facility: MAMC
Associate Investigator(s): COL Kelly J. Faucette, MC
Start - Completion: Funding:
11/17/2003 - Aug 2008 COG/POG via The Geneva Foundation
Periodic Review:
7/27/2005
Study Objective: (1) To determine the therapeutic activity (response rate and time to CNS
progression of intrathecal Topotecan in patients with recurrent or refractory neoplastic meningitis.
(2) To further assess the safety/toxicity of intrathecal Topotecan in the treatment of patients with
neoplastic meningitis. (3) To evaluate the concentration of matrix metalloproteinases (MMPs) in
the CSF of patients with recurrent or refractory neoplastic meningitis.
Technical Approach: A Phase II study for children and adolescents, 1-21 years of age with
neoplastic meningitis using Topotecan administered directly into the cerebrospinal fluid to
stabilize or shrink the cancer and give relief of cancer symptoms.
Progress: COG permanently closed this protocol 7 April 2006, due to low accrual. No patients
enrolled at MAMC.
337
Detail Summary Sheet
Date: 30 Sep 06 Number: 206045 Status: Completed
Title: The Pontine Valentine Leucocidin Virulence Factor in Staph Aureus Disease: A
Retrospective Study Analyzing CA-MRSA Incidence and Clinical Severity
Principal Investigator: CPT Ashley M. Maranich, MC
Department: Pediatrics Facility: MAMC
Associate Investigator(s): COL Mary P. Fairchok, MC; MAJ Steven D. Mahlen, MS
Start - Completion: Funding: Periodic Review:
1/19/2006 - Jun 2006 DCI N/A
Study Objective: Primary objectives are to determine the proportion of Panton-Valentin
leukocidin (PVL) positive strains of Staphylococcus aureus isolated in the MAMC Clinical
Microbiology Lab and to determine if PVL positivity is correlated with CA-MRSA strains.
Secondary objectives are to compare the clinical course of infections with PVL positive strains and
PVL negative strains through chart review.
Technical Approach: 538 clinical isolates of S. aureus have been tested by the MAMC clinical
microbiology lab for PVL toxin positivity by real-time PCR. This study proposes to access these
results and exclude duplicate isolates from the same infection as well as isolates that were
obtained for surveillance purposes only, then determine the proportion of isolates that were PVL
positive and separately analyze the proportion that were PVL positive for CA-MRSA versus
nosocomial MRSA and MSSA strains. Antibiotic susceptibility (to include D-test status for
erythromycin inducible clindamycin resistance) will be accessed to categorize the strains as MSSA,
nosocomial MRSA and CA-MRSA.
Outpatient and inpatient charts will be assessed from patients corresponding to the S. aureus
isolates and reviewed for the following clinical parameters: severity of infection, type of infection,
need for hospitalization, antibiotic regimen prescribed, route of antibiotic administration (IV vs.
PO vs. both), necessity for incision and drainage, number of clinic and/or ED visits related to
infection, recurrence of disease, prescription of eradication regimen.
Progress: This protocol was reported completed in June 2006. Results: Complete data was
available for 331 of 407 samples (82%). MRSA was more likely to be PVL+ than MSSA (166/201;
81% versus 31/130; 24%), p=.001. Disease characteristics associated with all PVL- strains were the
same as the MRSA PVL+ subset, with the exception that there was no increased need for I&D in
the MRSA PVL+ versus PVL- strains. Although PVL+ strains were less likely to require
hospitalization, they were associated with more outpatient visits than PVL- strains (3.56 versus
2.55, p<.02).
Conclusion: PVL is more likely to be associated with methicillin-resistance and community-
acquired SA infections. However, the study found that PVL+ strains were less likely to cause
invasive disease needing IV antibiotics or hospitalization. Controlling for MRSA+, PVL+ strains
were also no more likely to require I&D than PVL- strains. However, PVL does seem to cause a
higher healthcare burden with more recurrence and an increased number of outpatient visits.
338
Detail Summary Sheet
Date: 30 Sep 06 Number: 204040 Status: Ongoing
Title: National Cystic Fibrosis Foundation Patient Data Registry
Principal Investigator: COL (Ret) Donald R. Moffitt, MD
Department: Pediatrics Facility: MAMC
Associate Investigator(s): Dana A. Winter, C.R.T.
Start - Completion: Funding: Periodic Review:
2/6/2004 - Indef DCI 1/13/2006
Study Objective: (1) Monitoring epidemiologic trends in the population for CF patients in the US
through data collection and entry into the NCF Foundation Patient Registry. (2) Assist in
development of therapeutic advances responsible for the improved survival of cystic fibrosis
patients.
Technical Approach: The CF Patient Data Registry will include patients with cystic fibrosis who
are cared for at CF Care Centers throughout the U.S. Locally, this project will include patients
from the CF Care Center at Madigan Army Medical Center, which currently cares for 27 CF
patients. When a patient and/or parent gives written consent to be included in the registry,
updates of the patient's medical information will be sent to the CF National Patient Registry. The
information that is sent to the National Patient Registry includes patient name, date of birth,
social security number, and zip code of residence. Personal identifiers allow the CF National
Patient Registry to track information for patients who receive care at more than one CF center or
who move between CF centers. Patients have the choice of participating in the registry without
sending the patient's social security number to the CF National Patient Registry. Other
information that is sent to the CF National Patient Registry includes the following: specifics of
diagnosis (e.g., diagnosis date, sweat test results, genotype); clinical status (e.g., presence of
complications, transplant status); test results (e.g., pulmonary function tests, microbiology
cultures); nutritional status (e.g., height, weight, nutritional supplements, pancreatic enzyme use);
treatment information (e.g., hospitalizations, home therapies, use of new therapies ); participation
in clinical trials; and demographic data (e.g., educational status, marital status, employment
status, and insurance coverage).
Progress: This database protocol remains open to enrollment, with 18 patients enrolled MAMC,
none during FY06. Patient data continues to be collected and submitted to the Cystic Fibrosis
Foundation on MAMC patients enrolled.
339
Detail Summary Sheet
Date: 30 Sep 06 Number: 204028
Status: Ongoing
Title: Pediatric Intubation Training Utilizing the Ferret (mustela putorius furo) Model
Principal Investigator: LTC Robert A. Puntel, MC
Department: Pediatrics
Facility: MAMC
Associate Investigator(s): MAJ Catherine Kimball-Eayrs, MC
Start - Completion: Funding:
12/17/2003 - Dec 2006 DCI
Periodic Review:
11/8/2006
Study Objective: This is a training protocol using a ferret model to teach physicians and other
health care professions how to endotracheally intubate (i.e. place a plastic tube in the windpipe)
neonates and infants. The training is part of a two-day course in pediatric life-saving techniques;
the class is called Pediatric Advanced Life Support (PALS) and is developed by the American
Heart Association. PALS is offered through the Department of Emergency Medicine two to four
times a year.
Technical Approach: Students will complete classroom instruction in principles and techniques
of pediatric life support. The students will then practice techniques, include endotracheal
intubation, on mannequins. Following this practice, students will intubate an anesthetized ferret,
which more closely simulates the respiratory anatomy and reflexes of a human child than does a
mannequin. Up to six ferrets will be used for each training session and each ferret will serve to
train four physicians or other health care providers. The ferrets will be fully anesthetized and will
experience no pain during the procedure; they will be closely monitored and observed by a member
of the veterinary staff. During the procedure, each of the course participants will learn to place a
small plastic tube through the mouth and into the trachea (windpipe) of an anesthetized ferret
with the assistance of a small, lighted metal blade called a laryngoscope. The investigators, other
course instructors, and veterinary staff will directly supervise the procedure. If any ferret is
traumatized or shows signs of problems with the anesthetic drugs, the procedure will be stopped
on that animal. No animal will undergo more than seven intubation attempts. After the training
session is complete, the animals will be allowed to wake up from anesthesia and will be returned
to their usual housing at the MAMC Animal Facility. In the first days following the procedure, the
ferrets may experience a mild sore throat, and they will be offered moist food as needed. Ferrets
will be housed and maintained according to standard animal husbandry protocols.
Progress: Four PALS courses were held in FY 2006 with 88 medical personnel successfully
trained using many simulators and 10 ferrets for tracheal intubation training. With the new
SimBaby model, ferret use is less than in previous years. Expect to eventually phase out use of
live animals due to the quality of simulation trainers becoming available. Four labs are planned
for FY 2007.
340
Detail Summary Sheet
Date: 30 Sep 06 Number: 203046 Status: Ongoing
Title: Telemedicine Based Ultrasound for Detecting Neonatal Heart Disease in Babies at
Remote Military or Native American Health Care Facilities
Principal Investigator: LTC Robert A. Puntel, MC
Department: Pediatrics Facility: MAMC
Associate Investigator(s): COL James B. Kinney, MC; COL David T. Estroff, MC; David J.
Sahn, MD; COL (Ret) Edward R. Carter, MD; Mark D. Reller, MD
Start - Completion: Funding: Periodic Review:
7/22/2003 - Dec 2006 DCI via Grant 1/24/2006
Study Objective: This impact and outcomes research proposal will specifically test the hypothesis
that a method for reliable and rapid assessment of newborn infants at risk for heart disease can be
developed for telediagnosis using a small hand-held ultrasound system with an appropriate high
frequency transducer. The unique setting will be that the healthcare professional performing the
examination may not be a cardiologist or a fully trained echocardiographer, but the examination
will be monitored, supervised and guided using telemedicine links which will also allow control of
the scanning system settings by the remote supervisor who is an expert Pediatric
Cardiologist/echocardiographer.
\The program will assess diagnostic accuracy as the primary outcome variable and time to
diagnosis, incidence of unnecessary transport and length of stay during initial hospitalization
including transfer when it occurs, as secondary medical outcomes. Diagnosis will be established by
testing at a referral center or examination and ultrasound performed by the expert consultant on a
follow-up visit occurring at the referral site. In addition to any diagnostic findings of significance
which are missed, we will survey and document adverse events in the patient's subsequent course,
both medical and social (e.g: parent/baby separation, parental anxiety). Each infant will be
followed for 3 months from the time of the initial diagnosis encounter and will be compared to
historical controls. Finally, our study will also include a financial outcomes/cost analysis.
Technical Approach: This is a prospective, non-randomized, case-control study with
measurements obtained at baseline (entry into the study) and three months later. Source data will
consist of ultrasound images of the heart transmitted electronically from a remote site to a medical
center where they will be read and interpreted. Non-transmitted U/S images and data abstracted
from the infant's medical record will be recorded. Data will be obtained at baseline and three
months following baseline.
Recruitment and training of health care professionals: two individuals - a pediatrician, family
practitioner or obstetrical nurse from each designated participating center will be identified.
Initial training in the use of handheld ultrasound systems will occur at MAMC by Drs. Kinney and
Puntel and will consist of 2 days of classroom and individual hands-on instruction. A primer on
ultrasound instrumentation and methods for performance of cardiac ultrasound will be prepared
by Drs. Sahn, Kinney and Puntel. Infants whose families consent will be examined by the
attending pediatric cardiologist and have hands-on scanning performed by the trainees under his
supervision as the infant's condition allows.
When the portable scanner becomes available for each center and the Telemedicine link is
installed and activated, one of the four pediatric cardiologists staffing this program will visit with
the trainees at each institution to bring the scanner and operate the telemedicine link, see
patients and observe the trainees performing ultrasound examinations, especially in newborns.
They will certify on that examination and/or by follow-up observation of Telemedicine observed
341
studies by those healthcare provider-trainees when they are qualified to activate their site and
enroll patients.
Enrollment of patients will begin when all training has been completed and each center has
completed its own IRB process. Other care of and testing of the infant will be performed as
necessary by the hospital staff and results will be extracted from the patient's medical record.
Physical examination, EKG, and/or X-ray will be used, as routinely in a neonatal setting, for
identification of potential signs, symptoms, physical examination findings, EKG or radiologic
findings of congenital heart disease. Cyanosis will be detected by saturation meter and/or blood
gases as necessary. These are part of routine Level II nursery care for newborn infants and will
not be altered by the study. These protocols and methods may be specific to the site and
documented in the approval of these sites as level 2 or level 3 nurseries.
Progress: This protocol remains ongoing and open to enrollment, with 44 subjects enrolled at
MAMC for training purposes; 19 in FY06. An additional ten subjects enrolled at Bassett in FY06,
all subjects received a TeleECHO diagnosis confirmed 100% with follow-up conventional
echocardiography. One patient was diagnosed with Tetralogy of Fallot; underwent heart surgery
and is doing well. Twelve TeleECHO training sessions have been completed and 17 doctors
trained; three sessions and seven doctors in FY06. Doctors Kinney, Puntel, and Sahn are now
privileged to practice telemedicine at all sites except Yukon. All sites, except Yukon, have received
the necessary medical equipment for the study and arrangement are beginning to swap out
equipment per CRAD A/SOW. At this time Bassett, Weed, American Native, Elmendorf, and
Bayne-Jones have received IRB approval. Blanchfield will resubmit to the IRB once a new PI
completes all requirements. Oak Harbor and Bremerton's protocol is scheduled for another review
December 13, 2006 at Naval Medical Center San Diego. Yukon is still on hold due to staff
constraints. HSRRB is currently reviewing all IRB approved protocols. Madigan, Bassett, Weed,
American Native, and Bremerton have received approvals to connect to local area networks.
342
Detail Summary Sheets
Department of Pharmacy
343
Detail Summary Sheet
Date: 30 Sep 06 Number: 206092 Status: Completed
Title: Assessment of LDL-Cholesterol Goal Attainment Among Patients at a Very High Risk For
Secondary Cardiovascular Events in a Pharmacist-Managed Lipid Clinic
Principal Investigator: Helen S. Booth, PharmD
Department: Pharmacy Facility: MAMC
Associate Investigator(s): Emily V. Leaf, PharmD; Terri G Foster, MA, R.Ph
Start - Completion: Funding: Periodic Review:
5/22/2006 - May 2006 DCI N/A
Study Objective: To identify patients at very high risk for secondary cardiovascular events who
are unable to attain the newly recommended LDL-cholesterol goal, and to determine the reasons
for them not being able to attain their goal.
Technical Approach: All patients treated by Madigan Army Medical Center Internal Medicine
Lipid Clinic during the study period will be considered for analysis. Internal Medicine Lipid
Clinic's Access™ database and the health system's electronic medical record system (AHLTA,
ICDB, CHCS) will be used for data collection (patient age, gender, cardiovascular risk factors,
LDL-cholesterol level, anti-lipid medication therapy, and reported adverse medication events).
Excel™ database will be used to maintain collected data. Patients meeting the inclusion criteria
will be identified from the data collection and chart reviews conducted on patients meeting the
inclusion criteria. The number of patients identified to be at very high risk for secondary
cardiovascular events, the percentage of patients attaining their new LDL-cholesterol goal,
medications utilized to attain the goal, and the documented reasons for patients not being able to
attain the goal will be reported.
Progress: A total of 145 patients were identified to have LDL-C goal of < 70. Seventy-five patients
have reached their goal and 70 patients have not reached their goal. Of 75 patients who reached
their goal, 41 % was on a statin monotherapy, 3% on other monotherapy, 1% on no medications,
and the rest of patients were on a combination therapy. Of 70 patients who did not reach their
goal, 63% were in titration phase, 26% had no further treatment options, 10% were lost to follow¬
up, and 1% was non-compliant. This data was presented at American Society of Health- Systems
Pharmacists Summer Meeting 2006.
344
Detail Summary Sheets
Department of Preventive Medicine
345
Detail Summary Sheet
Date: 30 Sep 06 Number: 206056
Status: Completed
Title: Will Power: Is Personal Motivation Associated with Retention
in the Army?
Principal Investigator: CPT Hieu V. Hoang, MC
Department: Preventive Medicine
Facility: MAMC
Associate Investigator(s): ETC Andrew R. Wiesen, MC
Start - Completion: Funding:
1/31/2006 - Jun 2006 DCI
Periodic Review:
N/A
Study Objective: To determine the association between personal motivation and retention in the
Army among Soldiers processed through the Physical Disability Evaluation System.
Technical Approach: Cases will be randomly selected from Fort Lewis' electronic archive
database for years 2001-2005 and self-identifiers used to match subjects with their paper records.
Once the study is completed, self-identifier information will be omitted from the database. A
limited database will be constructed for this study to include subjects' sex, age, marital status,
rank, MOS, LOS, AD or reserve status, medical diagnosis, and motivation.
Progress: This protocol was reported completed in June 2006. The Medical Board is an
administrative process whereby Soldiers with a medical disability are evaluated to determine
fitness for duty. This cohort study attempted to better understand the role of personal motivation
and its associate with retention in the Army. We postulated that personal motivation is positively
correlated with retention. Logistic regression was used to evaluate predictors of retention in
Soldiers with a disability undergoing the medical board process. Self-expressed motivation as
measured by a single question was the strongest predictor of fitness determination. Motivation
was highly influential in 6 cases where the PEB had recommended separation, however all 6 cases
indicated a desire to remain on active duty and were found fit at the end. In addition, older age,
active duty status, MOS of combat support service, and medical diagnosis were found to be
statistically significant predictors of retention. It is difficult to say if the studied question truly
captures one's motivation, and research is warranted to better assess motivation more accurately.
346
Detail Summary Sheet
Date: 30 Sep 06
Number: 206066
Status: Completed
Title: Self Identification as a Predictor of Subsequent Mental Health Diagnosis
Principal Investigator: LTC Victoria R. Hughes, MC
Department: Preventive Medicine
Facility: MAMC
Associate Investigator(s): None.
Start - Completion:
3/22/2006 - May 2006
Funding:
DCI
Periodic Review:
N/A
Study Objective: To determine if an association exists between self-identification of a mental
health concern and the diagnosis of a psychiatric disorder by a psychiatrist or psychologist among
Soldiers returning from Operation Iraqi Freedom (OIF).
Technical Approach: All Soldiers with 1-25 Stryker Brigade returning from OIF, will be followed
to see if at any time during the 5 month (October 2005 to March 30, 2006) post-deployment
timeframe they were diagnosed with any of the following specific psychiatric diagnosis
[International Classification for Diseases-9th edition] (ICD-9) code(s): adjustment disorder (309,
309.0 -.9), PTSD (309.81), depression (296.2, 296.3 300.4, 311), acute stress disorder (308, 308.0 to
.3), anxiety/panic attacks (300.00, 300.01, 300.02, 330.21) and suicidal ideation (300.9) by a
provider specifically trained in the area of behavioral/mental health i.e. psychologist or
psychiatrist. MAMC Health Outcomes Management Division will provide the dates for the
following: completion of post-deployment health assessment (DD 2796), SWAPP and the
psychiatric diagnosis.
Progress: Results: Of the original 3,151 in the Brigade that returned from Operation Iraqi
Freedom (OIF), 250 (8%) were eliminated because they had been previously diagnosed with a
mental health illness. This left 2,901 to be in the study group to take the initial post deployment
health risk assessment (PDHRA) upon return from OIF. Of these 2,901, just over 57% (1,672)
remained on the military installation for the entire 14 month study period. The median age was
26; the most common age was 24, with an age range of 19 to 54. Fifty percent were white, and
nearly 37% were single. A majority of the Soldiers were enlisted (86%), with a high school
education or less (57%) and only 4% were female. Demographic information that was not
completed by the Soldiers on the questionnaires is labeled as unspecified in their respective
categories. After completion of the Post Deployment Health Risk Assessment (PDHRA), 33 (2.0%)
Soldiers were referred to see a mental health provider. Of those referred, 7 (21.2%) were diagnosed
with a mental health illness and 26 (78.8%) were not diagnosed with a mental health illness. Of
the 1,639 (98.0%) who had not indicated a mental health concern and therefore had not been
referred to see a mental health provider 108 (6.6%) were later diagnosed with a mental health
illness, and 1,531 (93.4%) were not diagnosed during the 14 month study period at the military
installation's medical facility. This study looked at the six most common mental health diagnoses
diagnosed in those who have had war/combat-zone experience, a total of 115 diagnoses made from
October 2004 to December 2005. Adjustment disorder was diagnosed in 47 Soldiers, depression in
26, anxiety/panic attacks in 25, PTSD in 10, and acute stress reaction in 7. Of the 10 Soldiers
diagnosed with PTSD, none were self identified. Suicidal ideation was not self identified by any of
the Soldiers, nor was suicidal ideation diagnosed in any of the Soldiers.
Conclusions: This study shows that early self identification of mental health concerns is not
predictive of a clinical diagnosis from a mental health provider at a military clinic within 14
months. There were more mental health diagnoses made for those who did not initially self
identify with having a mental health concern when taking the PDHRA. This suggests the idea that
some mental health symptoms develop over time after a traumatic experience. A second, later,
347
assessment may need to be done to improve its predictive value. The mental health diagnoses
made were relatively rare; 115 (6.9%) out of a cohort of 1,672. These results are low compared to
the 12% diagnosed in Hoge's study published March 2006. The number of positive self
identifications for a mental health concern is minimal at 33, compared to the number of non self
identifications of a mental health concern at 1,639. Single Soldiers appear to be more at risk of
being diagnosed with a mental health illness. Being married possibly helps a soldier in coping with
mental health concerns. Only 5% of married Soldiers had a positive mental health diagnosis,
compared to 9% of single Soldiers and 95% married Soldiers were not diagnosed with a mental
health illness. Marriage most likely provides for a good support system that is accessible, while
those who are not married may have support systems that are less easily available. None of the
Soldiers diagnosed with PTSD were initially self identified at the time the PDHRA was completed.
This is most likely the case because it may take up to several months after the traumatic event for
someone to actually develop signs and symptoms of PTSD. It is also possible that mental health
providers do not want to give a soldier a mental health diagnosis right away.
On site mental health diagnoses are probably the tip of iceberg for post- combat mental health
illness, given how few diagnoses were made. Assessments done immediately upon return miss
many Soldiers. Signs and symptoms for post traumatic mental health illnesses do not manifest
immediately. Mobility of the cohort limited the ability to have continuity of care. Many Soldiers
were not available to take the second health risk assessment given at 3 to 6 months after return
from OIF. This may have prevented some Soldiers from self identifying a mental concern and
possibly from even realizing that maybe they were having symptoms when asked specific mental
health questions. Of those 1,672 around for the entire 14 months, only 799 took the Health Risk
Assessment II. Why the compliance was so low in taking the second assessment is not completely
clear. Several possible reasons are that Soldiers were out in the field training, that they were on
vacation or sick, or that they just did not want to go to take the assessment. Once it was noticed
that the numbers were low, those responsible for conducting the assessment decided to take the
assessment to the Soldiers. Effective mental health programs for military service members are
essential. The military command needs to be aware and responsive to young, single, low ranking
Soldiers returning from a war/combat-zone who may experience more mental health issues then
other Soldiers.
348
Detail Summary Sheet
Date: 30 Sep 06 Number: 206074
Status: Completed
Title: Military Rank as a Risk Factor for Type 2 Diabetes
Principal Investigator: LTC Carol A. Moores, MC
in Military Spouses
Department: Preventive Medicine
Facility: MAMC
Associate Investigator(s): None.
Start - Completion: Funding:
3/30/2006 - May 2006 DCI
Periodic Review:
N/A
Study Objective: To determine whether rank is associated with the likelihood of type 2 diabetes
mellitus in the spouses of active duty military.
Technical Approach: This study will generate a Case Group of 400 spouses with ICD-9 codes
consistent with Type 2 Diabetes and generate a Control Group of 400 spouses that do not have an
ICD-9 code consistent with any type of diabetes. (Both groups have been seen in primary care
within the past 12 months.) Variables to be generated include age, gender, sponsor rank, number
of people in family, race/ethnicity. Outpatient records will be reviewed for confirmation that the
provider(s) have given a working diagnosis of Type 2 diabetes (rather than Type 1 Diabetes or
other diagnosis). A subject will be excluded if the record does not indicate Type 2 Diabetes. All
records will also be reviewed for BMI and tobacco use information. Data will be summarized using
descriptive statistics. Data will be analyzed using logistic regression. Modeling will be used to
determine the most important predictive variables and the relationships between those variables.
Progress: This protocol was reported as completed in June 2006. A chart review was conducted of
840 health records with 680 meeting the inclusion criteria. Results showed no evidence of an
association between the rank of an active duty military service member and the likliehood of type
2 diabetes in the spouse.
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Detail Summary Sheet
Date: 30 Sep 06 Number: 206033 Status: Completed
Title: Hazards to Hearing and Threshold Shifts: The Results of Deployment to a Combat
Environment
Principal Investigator: MAJ Troy W. Ross, MC
Department: Preventive Medicine Facility: MAMC
Associate Investigator(s): William Daniell, MD; LTC Andrew R. Wiesen, MC
Start - Completion: Funding: Periodic Review:
12/14/2005 - Jun 2006 DCI N/A
Study Objective: This proposed study will determine the incidence of hearing loss in the cohort
over the period of deployment, use a survey tool to establish correlations between hearing hazards
and measured threshold shifts, use a survey to establish the patterns of use of hearing protection
and use the findings of this study to improve the Military's hearing conservation program.
Technical Approach: Baseline screening audiograms will be obtained on 4000 active duty
Soldiers prior to deployment and follow up exams will be completed after their return.
Additionally, a questionnaire will be administered to the group as part of their post deployment
screening to determine how hearing protection was used, the noise hazards experienced, and what
ototoxic exposures the soldiers may have had. The incidence of hearing loss will be correlated to
protection measures that were used and hearing hazards that were experienced.
Progress: This protocol was reported completed in June 2006, with 3,231 Soldiers meeting
inclusion criteria and identified as members of the 1st Stryker Brigade during the post deployment
health screening. Of those, 2,370 were offered surveys, and 1,176 surveys were returned (49%
response). The cohort was overwhelmingly male and about half were in direct combat occupations.
The length of service categories showed an unequal distribution with relatively more Soldiers in
the earlier years of service, but this corresponds to the distribution of the general Army
population.
Results: 623 members of the cohort were identified as having an STS. This yields an annual
incidence of 19.2%. The STS rate was similar for male and female soldiers, slightly higher for
combat soldiers than those in support positions, and progressively lower with longer length of
service. The STS rates ranged from 15.4% to 21.8% in the eight non-combat jobs categories, but the
differences were not statistically significant
350
Detail Summary Sheet
Date: 30 Sep 06 Number: 205099
Status: Ongoing
Title: CD4+ T Cell Epitope Identification for Protective Antigen of Bacillus Anthracis
Principal Investigator: LTC Andrew R. Wiesen, MC
Department: Preventive Medicine
Facility: MAMC
Associate Investigator(s): CPT Michele A. Soltis, MC; William W. Kwok, Ph.D.
Start - Completion: Funding:
12/13/2005 - Mar 2007 Benaroya Research Institute via CRADA
Periodic Review:
6/20/2006
Study Objective: To describe CD4+ T cell epitopes of the Protective Antigen of Bacillus.
Technical Approach: This is a purely descriptive, basic science study, intended to further
understanding of how the human immune system responds to anthrax vaccine. Up to 30
individuals who have received at least 3 doses of anthrax vaccine will be asked to undergo HLA
typing (cheek swab). Those with a common HLA type will be asked to give a sample of blood
(maximum of 120 cc) for epitope mapping of CD4+ cells. The participants will be drawn from the
Fort Lewis active duty and former active duty population. Data analysis will be from flow
cytometry methods. As there is no formal hypothesis testing, there will be no formal statistical
analysis.
Progress: This protocol remains open to enrollment with 35 patients enrolled at MAMC; 26
subjects had HLA typing completed and nine have HLA typing in progress. Of the 26 who had
HLA typing completed, one was HLA non-compatible, two departed the Fort Lewis area prior to
blood draws, and two blood draws are pending. Of the 21 subjects who had blood drawn for the
study, six were asked to submit a second sample, and three were asked to submit a third sample.
There have been no significant adverse events during the study. One subject suffered a momentary
loss of consciousness during the blood draw, but recovered uneventfully. Recruitment continues.
There has not yet been a patient with DR-8 antigen enrolled in the study.
351
Detail Summary Sheets
Department of Psychiatry
352
Detail Summary Sheet
Date: 30 Sep 06 Number: 204089 Status: Ongoing
Title: A Placebo-Controlled Trial of Prazosin vs. Paroxetine in Combat Stress-Induced
Nightmares and Sleep Disturbance
Principal Investigator: LTC Kris A. Peterson, MC
Department: Psychiatry Facility: MAMC
Associate Investigator(s): MAJ Christine M. Daly, MC; LTC Michael E. Doyle, MC; Larry G.
Knauss, Ph.D.; Elaine R. Peskind, M.D.; Miles M. McFall, Ph.D.; Murray A. Raskind, M.D.;
David J Hoff, PA-C; Kimberly L Hart, PA-C; Michele Klevens, MA; James O'Connell; Hollie A
Holmes; Kirsten Rohde, RN, BSN
Start - Completion: Funding: Periodic Review:
10/29/2004 - Sep 2008 VA via MIPR 6/27/2006
Study Objective: The primary goal of this study is to evaluate the efficacy and tolerability of the
alpha- 1 adrenergic antagonist prazosin (available commercially since 1972) compared to placebo
for combat stress-related nightmares, sleep disturbance and overall function in recently combat-
exposed returnees from Operation Iraqi Freedom (OIF) and Operation Enduring Freedom (OEF).
A secondary goal is to evaluate the effects of the selective serotonin reuptake inhibitor (SSRI)
paroxetine on behavioral symptoms and overall function in this population.
Technical Approach: Sample Population/Sample Size includes 90 male and female returning
troops from OIF and OEF who manifest persistent combat stress-related nightmares and sleep
disturbance. Methods: responses of combat stress-related nightmares, sleep disturbance, and over
all stress-related symptom severity will be compared among groups randomized to the alpha- 1
adrenergic antagonist prazosin, the SSRI paroxetine, and placebo in a 12-week, double-blind
study. Outcome Variables: Clinician-Administered PTSD Scale (CAPS) item 2 "recurrent
distressing dreams," item 13 "disturbed sleep," and total CAPS score; Pittsburgh Sleep Quality
Inventory; Clinical Global Impression of Change; Hamilton-Depression Rating Scale total scores.
Data Analysis Plan: Data will be analyzed for significant differences in outcome variables among
treatment groups using generalized estimating equations.
Progress: This protocol remains open to enrollment. During FY06, 23 subjects were randomized;
thirteen were screen failures (eight no-showed for screen). Of the 23 subjects randomized, one is
currently participating, eight completers (2-prazosin, 3-paroxetine, 3-placebo), fourteen non¬
completers (eight lack of compliance, three time/scheduling conflicts, one deployed, one worsening
symptoms, one terminated by investigator at baseline). There were no adverse events reported.
353
Detail Summary Sheet
Date: 30 Sep 06 Number: 206011 Status: Ongoing
Title: Prazosin for the Treatment of Trauma Nightmares in PTSD
Principal Investigator: LTC Kris A. Peterson, MC
Department: Psychiatry Facility: MAMC
Associate Investigator(s): Murray A. Raskind, M.D.; Elaine R. Peskind, M.D.; Miles M.
McFall, Ph.D.; Larry G. Knauss, Ph.D.; Bradford L. Felker, MD; Jessica W. Cook, PhD
Start - Completion: Funding: Periodic Review:
12/22/2005 - Sep 2010 DCI 10/24/2006
Study Objective: The primary goal of this study is to evaluate the efficacy and tolerability of the
alpha- 1 adrenergic antagonist prazosin (available commercially since 1972) compared to placebo
for combat stress-related nightmares, sleep disturbance and overall function in recently combat-
exposed returnees from Operation Iraqi Freedom (OIF) and Operation Enduring Freedom (OEF).
Technical Approach: Men and women (120 subjects) with both persistent (> one month
duration) troublesome combat stress-related nightmares (CAPS "recurrent distressing dreams"
item 5 [maximum score = 8]) and sleep disturbance (CAPS "difficulty falling or staying asleep"
item 5 out of a maximum score of 8) who are in good general health and are not taking
exclusionary medications are eligible for this study. This is a double-blind, placebo-controlled
treatment study of prazosin in combat-exposed persons who have trauma-associated nightmares
and sleep disturbance. After a titration period (1-8 weeks in duration) to reach "optimum" dose (up
to a maximum of 25 mg/day of prazosin for subjects who weigh less than 250 lbs and 30mg/day of
prazosin for subjects who weigh more than 250 lbs), subjects will come to the clinic every two
weeks to undergo efficacy evaluation. After the treatment period, the blind will be broken and
subjects will be referred to their primary mental health provider for further treatment. Subjects
will come in to the clinic for follow-up visits 12 and 26 weeks after the treatment period ends.
Outcome measures will include Clinical Global Impression of Change (CGIC), Recurrent
Distressing Dreams and Difficulty Falling and Staying Asleep items of the Clinician-Administered
PTSD Scale (CAPS), PTSD Dream Rating Scale (PDRS), Nightmare Frequency Questionnaire
(NFQ), Insomnia Severity Index (ISI) and Pittsburgh Sleep Quality Index (PSQI). Depression and
quality of life will also be assessed with the Hamilton Depression Rating Scale (HAM-D) and
Quality of Life Index (QOLI). The primary intent-to-treat (ITT) efficacy assessment will compare
the prazosin and placebo group's CGIC scores at 8 weeks. Since response is not anticipated to be
progressive, any missing observations will be imputed using the last observation carried forward
(LOCF) procedure. The CAPS Recurrent Distressing Dreams and Difficulty Falling or Staying
Asleep items, total CAPS, Mississippi Scale, PSQI, ISI, PDRS, NFQ, Ham-D, and QOLI item will
be analyzed as a continuous response measure. Rates of change in response measures will be
evaluated according to ITT between the prazosin and placebo groups using an analysis of
covariance model with the 8-week values as the response measure and baseline measure as a
covariate along with any potential confounding variables. The median time to study
discontinuation (in those patients who drop out secondary to unacceptable adverse effects) will be
compared between the two treatment groups using the Cox proportional hazards model.
Frequency of individual adverse event occurrence will be compared by chi square and adverse
event severity by unpaired t-test between prazosin and placebo conditions to estimate the clinical
significance of potential prazosin adverse effects.
Progress: This protocol remains open to patient entry, with twelve subjects consented during
FY06. Two subjects did not begin study medication after randomization (the blind was not broken
in these two cases). Three subjects (2-prazosin, 1-placebo) were removed from the study due to
354
compliance issues. One subject (placebo) withdrew at Week 04 due to relocation. One subject
(prazosin) withdrew at Week 08 due to relocation; and although blinded portion of the study was
complete, the subject was not seen for follow-up visits. Two subjects (2-placebos) completed the
blinded portion of the study and are currently active in follow-up. Recruitment is ongoing.
355
Detail Summary Sheets
Department of Psychology
356
Detail Summary Sheet
Date: 30 Sep 06 Number: 206062 Status: Ongoing
Title: Military Readiness Risks: Leader Perspectives Impact on Mandatory Addiction Referrals
Principal Investigator: Jolee N. Darnell, MSW, LICSW, CDP
Department: Psychology Facility: MAMC
Associate Investigator(s): Lori A. Loan, RNC, Ph.D.; Brenda M. Wilson, MS, LPA, CDP; Ross
A. Echterling, BS, CDP; Joseph D. Darnell, BA
Start - Completion: Funding: Periodic Review:
6/10/0063 - Mar 2007 DCI N/A
Study Objective: The goal of the research is to determine whether there are other interventions
or education that could be used to target and improve the referral rates and ultimately military
readiness.
Technical Approach: This proposal uses a qualitative research method approach to examine
questions related to the impact of leader attitudes and operational tempos on completion of
mandatory substance abuse referrals. Action research methods will be used, including ex post facto
review of existing data and interviews and focus groups with key stakeholders (Active Duty Fort
Lewis military leaders at the levels of platoon, company, battalion, and brigade). The researcher
will coordinate with the First Corps Surgeon's office and each Brigade Surgeon's office to recruit
focus group and individual interview volunteers from each Brigade size unit at the installation.
Recruitment requests will be made through the process of Officer Professional Development (OPD)
and Non-Commissioned Officer Professional Development (NCOPD) during required training on
health and health care related topics.
Following documented informed consent, the study will use interviews and focus group discussions
to generate information for the research questions. Discussion topics will include: participant
understanding of regulatory referral requirements, participant philosophy about alcohol and drug
use in the military; participant understanding of substance abuse and dependence; perspectives
about positive and negative aspects of the Army's mandatory substance abuse referral program;
participant perspectives on data trends; participant perspectives about relationships between
military mission requirements and mandatory substance abuse referral processes. Before focus
groups and interviews are conducted, specific dialogue will be validated for appropriateness by an
expert panel of line leaders and professionals involved in the referral process. The goal is to get the
experts to provide guidance and critique of the specific discussion topics to be used in the focus
groups and interviews.
Progress: Four individual interviews have been conducted. Three interviews and one focus group
have been scheduled 14 November 2006. The study has shifted to more interviews and less focus
groups, since military operations schedules during the summer months had an impact on ability to
schedule focus groups. The goal is to interview 15-30 military leaders individually or in groups
about their perspectives on substance abuse referral procedures. Transcription of interviews
conducted to date is reflecting some expected responses as well as perspectives not clear from data
analysis reviews prior to the interviews. One perspective that has emerged reflects the level of
knowledge or training received by unit leadership about requirements and benefits of using the
substance abuse referral process. Group and individual interviews/data collection is projected to be
completed by 1 December 2006. Transcription and preliminary data analysis is projected to be
completed by 31 Dec 2006.
357
Detail Summary Sheet
Date: 30 Sep 06 Number: 205019 Status: Ongoing
Title: Theory-Guided Anticipatory Guidance
Principal Investigator: Patti L. Johnson, Ph.D.
Department: Psychology Facility: MAMC
Associate Investigator(s): Christine Moon, PhD
Start - Completion: Funding: Periodic Review:
12/3/2004 - Oct 2005 UW/PLU 11/30/2006
Study Objective: The objective is to test the application of the prevailing psychological theory of
persuasion on information delivery to mothers of young infants.
Technical Approach: This study will test the use of the Elaboration Likelihood Model (ELM) of
persuasion on attitude change of 200 mothers of newborn infants regarding early shared reading
with their infants. The two independent variables are 1) two levels of participants' live birth (para)
status and 2) two formats of a brief education intervention. The education intervention will be
administered during the last 10 minutes of a 20-minute session to be scheduled after the daily
Mother/Baby Unit discharge class. During the first 10 minutes, informed consent will be obtained
and three brief questionnaires will be completed: a personal information questionnaire, the
Sensations during Pregnancy and Life Events Questionnaire, and a questionnaire on attitudes
about early shared reading. The effect of intervention will be assessed two months later by re¬
administering the questionnaire on attitudes about early shared reading. Para status is a marker
for level of distraction from parenting the new baby, important for ELM application. Verification of
level of distraction will be made by using the Sensations during Pregnancy and Life Events
Questionnaire.
At the conclusion of data collection, there will be 40 mothers in each of the 4 intervention groups (2
para statuses X 2 formats.) A control group (n=40) will receive general information on
speech/language development. The dependent variable will be difference scores on the pre- and
post-intervention questionnaires on attitude about early shared reading, and the difference scores
will be analyzed using analysis of variance. It is predicted that there will be a statistically
significant interaction effect between para status and intervention format. Further, difference
scores of both intervention groups will be higher than control group scores. Results of the
experiment are expected to inform the practice of information delivery to patients, specifically in
anticipatory guidance in pediatrics.
Progress: This protocol remains open to enrollment with 149 participants enrolled to date, which
represent half of the 300 participants planned for this study. Virtually no data were collected since
December 2005 due to changes in personnel and lack of research funding for the project. Personnel
will become available for the project in January 2007 and data collection will resume.
358
Detail Summary Sheet
Date: 30 Sep 06 Number: 206088
Status: Ongoing
Title: Exposure to Death and Dying and Mental Health Response
Principal Investigator: Barbara A. Lucenko, PhD
in Operation Iraqi
Department: Psychology
Facility: MAMC
Associate Investigator(s): Shira Maguen, PhD; COL Gregory A. Gahm, MS
Start - Completion: Funding:
5/8/2006 - May 2008 DCI
Periodic Review:
N/A
Study Objective: To test a model demonstrating the relationship between exposure to death and
dying, mental health outcome, and functional impact following deployment to Iraq.
Technical Approach: The Health Risk Appraisal II (HRA-II) is administered 90 days post¬
deployment. Soldiers completed an automated version of the HRA-II in groups scheduled according
to specific Active Duty units. Groups were reportedly scheduled according to unit re-deployment
status. The screening may have occurred at any point between 60 and 120 days after returning
from deployment, although the typical timeframe has been reported as between 60-90 days. A data
transfer process serves to populate a secure Oracle database housed within the Army Behavioral
Health Technology Office. Algorithms written into software score the clinical scales and generate
reports for Behavioral Health (BH) routing and provider use. All soldiers are then seen by a BH
provider on site and follow up clinical referrals are made based on both screening and interviews.
Prior to analyses for this project, appropriate fields from the database will be copied stripped of all
identifying information (name, social security number, and contact information). The relevant
variables outlined in this proposal will be sent to the San Francisco VA Medical Center for the
specified data analysis. Dr. Maguen will not have access to any of the identifying information
(names and social security numbers, and contact information) at any point during the study. Also,
the data will continue to be owned by MAMC.
Progress: A data set was finalized, de-identified, and forwarded to Dr. Maguen for analyses. The
protocol remains ongoing as analyses are still in progress.
359
Detail Summary Sheet
Date: 30 Sep 06 Number: 206118 Status: Ongoing
Title: User Centered Design Feedback for the Virtual Iraq
Principal Investigator: CPT Greg M. Reger, MS
Department: Psychology Facility: MAMC
Associate Investigator(s): COL Gregory A. Gahm, MS; Mark A. Reger, PhD; John L. Miller,
MD; Barbara A. Lucenko, PhD; Albert A Rizzo, PhD; CPT Roberta L. Shepard, MC; Robert D.
Swanson, M.A.
Start - Completion: Funding: Periodic Review:
10/19/2006 - Jul 2007 TATRC N/A
Study Objective: To obtain user-centered design feedback from healthy, non-patient soldiers to
guide the project development of a virtual reality application (VR Iraq) intended for future use to
treat a wide range of possible traumatic combat experiences.
Technical Approach: Following consent, Soldiers will complete a brief demographic
questionnaire and PTSD Checklist, which is a validated PTSD screening tool. The consenting
investigator will review these documents and ensure that the participant meets
inclusion/exclusion criteria. In the case that the participant self-reports significant levels of
trauma related symptomatology, the investigator will discontinue formal participation in the
project and will offer to discuss their responses on the survey and escort participants to a private
location to talk (e.g., Behavioral Health Clinic or Soldier Readiness Service) to discuss options for
referral and treatment, if indicated. Participants who meet inclusion/exclusion criteria will utilize
the two VR scenarios. The current city scenario has the appearance of a desolate set of low
populated streets comprising old buildings, ramshackle apartments, warehouses, a mosque,
factories, and junkyards. The second scenario is a convoy scenario in which the user navigates
down paved and dirt desert roadways with occasional areas of vegetation, battle wreckage, and
debris. As soldiers navigate through these environments, the investigator will activate currently
available trigger stimuli. Currently, the VR Iraq allows the controller to introduce audio triggers
(i.e., incoming mortars, weapons fire, voices, wind, etc.) and audiovisual triggers (e.g., helicopter
flyovers). Total time utilizing the VR Iraq will be approximately 5 minutes.
Progress: This greater than minimal risk protocol received initial approval with stipulations
during the convened IRB meeting on 22 August 2006. Final approval was granted 19 October
2006.
360
Detail Summary Sheet
Date: 30 Sep 06 Number: 206077 Status: Ongoing
Title: Army Suicide Event Report: Data Analysis
Principal Investigator: Mark A. Reger, PhD
Department: Psychology Facility: MAMC
Associate Investigator(s): COL Gregory A. Gahm, MS; Barbara A. Lucenko, PhD
Start - Completion: Funding: Periodic Review:
4/10/2006 - Mar 2008 DCI N/A
Study Objective: To establish an effective and efficient model of risk assessment for suicide,
suicide ideation, and suicide attempts using existing data from the Army Suicide Event Report
(ASER).
Technical Approach: This study is a retrospective review and exploratory analysis of Soldiers
for whom ASER data exists. Initial review reveals 742 records as of November 2005. The study
will track suicide behavior for 2005-2007, using exploratory analyses to detect trends and risk and
protective factors.
Progress: A total of 1,128 Army Suicide Event Reports (ASER) have been submitted during FY06,
out of a total 1,616 that are in the database. Data collection continues, analyses have not been
conducted for this protocol to date.
361
Detail Summary Sheets
Department of Radiology
362
Detail Summary Sheet
Date: 30 Sep 06 Number: 202117
Status: Ongoing
Title: Intravenous Administration of 131 I-6-B Iodomethylnorcholesterol (NP-59) for Adrenal
Evaluation and Imaging
Principal Investigator: ETC Antonio G. Balingit, MC
Department: Radiology
Facility: MAMC
Associate Investigator(s): CPT Deborah E. Floyd, MS;
Jane E. Besich- Carter, BS, BCNP
COL (Ret) Jerome L. Billingsley, MD;
Start - Completion: Funding:
1/7/2004 - Jul 2003 DCI
Periodic Review:
8/29/2006
Study Objective: Clinical evaluation of NP-59 as a diagnostic agent for the detection of adreno¬
cortical disorders.
Technical Approach: The drug to be used in this study, NP-59, is investigational and will be
used under IND number 12605, which is held by the University of Michigan. This study will be
performed in humans of either sex only after complete evaluation by the Endocrinology Service of
MAMC. All female patients between the ages of twelve and fifty-five will have a serum B-HCG
determination except those who had a hysterectomy. Pregnant or lactating patients will be
excluded. This agent will be administered to children less than 18 years of age only for exceptional
reasons with the approval of the Chief, Nuclear Medicine Service and Chief, Pediatric
Endocrinology Service and only after other alternative procedures are determined to be
inappropriate. Ideally, studies in women of childbearing capability are performed during the first
10 days post-menses. NP-59 will be obtained in pharmaceutical form from the University of
Michigan Nuclear Pharmacy. In house quality control, including determination of radionuclidic
and radiochemical purity, will be performed on all shipments of NP-59 prior to human use. NP-59
will be administered by slow intravenous injection with a dose of 2mCi in adults, 15 UCi/kg in
children except where the benefit to risk ratio warrants a higher dose. Under no circumstances
will more than 2.2 mCi be administered. Lugol's solution, 5 drops twice daily starting one day
before injection and continuing for two weeks, will be used to block thyroid uptake of radionuclide.
Planar and SPECT images will be obtained on the 3rd, 4th and 5th days after injection using a
dual detector scintillation camera connected to an on-line computer. Studies will be performed in
accordance with the protocol "131 I-6-B iodomethylnorcholesterol." Informed consent will be
obtained prior to entry into the study.
Progress: No patients have been enrolled. The radiopharmaceutical is an 'orphan' drug and
infrequently utilized therefore has not been FDA approved. It can be procured only as an IND.
Nuclear Medicine Service has to keep a protocol ongoing in order to utilize the drug as the need
arises.
363
Detail Summary Sheet
Date: 30 Sep 06 Number: 206053 Status: Ongoing
Title: NSABP B-39 / RTOG 0413 A Randomized Phase III Study of Conventional Whole Breast
Irradiation (WBI) Versus Partial Breast Irradiation (PBI) for Women with Stage 0, I or II Breast
Cancer
Principal Investigator: LTC William B. Reece, MC
Department: Radiology Facility: MAMC
Associate Investigator(s): LTC John B. Halligan, MC; MAJ Joseph P. Brooks, MC; MAJ
Jasmine T. Daniels, MC; MAJ Angela G. Mysliwiec, MC; LTC David E. McCune, MC
Start - Completion: Funding: Periodic Review:
6/5/2006 - Feb 2011 SWOG via Henry M. Jackson Foundation N/A
Study Objective: Primary objective is to determine whether partial breast irradiation (PBI)
limited to the region of the tumor bed following lumpectomy provides equivalent local tumor
control in the breast compared to conventional whole breast irradiation (WBI) in the local
management of early stage breast cancer.
Secondary objectives are (1) to compare overall survival, recurrence-free survival, and distant
disease-free survival between women receiving PBI and WBI, (2) to determine whether PBI
delivered on 5 treatment days over a period of 5 to 10 days can provide a comparable cosmetic
results to WBI, (3) to determine if PBI produces less fatigue and treatment-related symptoms
compared to WBI, (4) to determine if perceived convenience of care is greater for women receiving
PBI compared to women receiving WBI and (5) to compare acute and late toxicities between the
radiation therapy regimens.
Technical Approach: This Phase III, randomized trial will enroll patients with stage 0 (DCIS) or
stage I or II invasive adenocarcinoma of the breast with no evidence of metastatic disease who
have undergone lumpectomy with cancer-free margins, and have no more than 3 positive axillary
nodes. Patients will be stratified according to disease stage, menopausal status, hormone receptor
status, and intention to receive chemotherapy. Following stratification, patients will be
randomized to receive WBI or PBI. WBI for this study will be standard techniques delivered over 5
to 7 weeks. PBI will utilize the technologies of high dose-rate multi-catheter brachytherapy, high
dose-rate single catheter balloon brachytherapy (MammoSite), and three-dimensional conformal
external beam radiation therapy. Patients randomized to receive WBI will receive chemotherapy,
if applicable, before their radiation therapy. Patients randomized to PBI will receive radiation
therapy before chemotherapy, if applicable. For patients who agree to blood and tissue studies,
blood will be submitted after randomization but before therapy begins and tissue blocks will be
submitted within 3 months after randomization. Patients will have follow-up visits at end of
radiation therapy, 4 weeks, 6 months, 12 months, every 6 months through Year 5, then annually
through Year 10. The first 482 patients who are having chemotherapy and the first 482 patients
who do not intend to receive chemotherapy will have the option of being included in a QOL and
cosmesis study. These patients will have 7 QOL questionnaires to complete during the course of
treatment and follow-up, and will have three sets of digital photographs taken of their breasts at
baseline, Year 1 and Year 3. RTOG will provide a web-based image management system for sites
to upload images as JPEG files. Each site will have restricted access to only their image archive,
and once images are uploaded they will only be accessible to NSABP reviewers. The primary
statistical endpoint for the study is diagnosis of in-breast tumor recurrence (IBTR). Regional and
distant failures and death prior to IBTR will be treated as competing risks. Contralateral breast
and non-breast secondary primary cancers will not be considered as competing risks. Secondary
endpoints include distant disease-free interval, recurrence-free survival and overall survival.
364
Progress: This protocol is open to patient entry, with no patients enrolled during FY06. A slow
down in recently diagnosed early stage breast cancer patients has occurred recently; this protocol
will remain ongoing to accrue patients over the next year.
365
Detail Summary Sheet
Date: 30 Sep 06 Number: 204069 Status: Ongoing
Title: SWOG RTOG 0212, A Phase II/III Randomized Trial of Two Doses (Phase Ill-Standard vs.
High) and Two High Dose Schedules (Phase Il-Once vs Twice Daily) for Delivering Prophylactic
Cranial Irradiation for Patients With Limited Disease Small Cell Lung Cancer
Principal Investigator: LTC William B. Reece, MC
Department: Radiology
Facility: MAMC
Associate Investigator(s): LTC John B. Halligan, MC
Start - Completion:
7/20/2004 - May 2007
Funding:
SWOG via Henry M. Jackson Foundation
Periodic Review:
4/10/2006
Study Objective: (1) To determine the impact of an increase in the total PCI dose on the
incidence of brain metastases at a minimum of 2 years of patient follow up; two PCI dose levels
will be compared: 25 Gy (standard dose PCI) versus 36 Gy (high dose PCI) in limited disease small
cell lung cancer (LD SCLC) patients in complete remission, whatever the initial treatment. (2) To
determine the impact of PCXI dose of overall and disease-free survival; (3) To determine the
impact of PCI dose on quality of life and late treatment sequel, 4) To determine the impact of PIC
dose and schedule on the incidence of chronic neurotoxicity, and (5) To determine the impact of
PCI dose and schedule on quality of life.
Technical Approach: About five to seven subjects per year would potentially eligible for this
protocol at Madigan Army Medical Center. The protocol randomizes subjects to receive one of three
doses of prophylactic cranial irradiation. Arm I subjects receive 2.5 G ray once daily for 10
fractions for a total of 25 G ray. Arm II subjects receive 2.0 G ray once daily for 18 fractions for a
total of 36 G ray. Arm III subjects receive 1.5 Gray once daily for 24 fractions for a total of 36 G
ray. The study will examine the incidence of brain metastases as the primary end point and assess
the cognitive and neurologic side effects of subjects on the above treatment doses and delivery
schedules through neurotoxicity/neuropsychological testing. The results of this study may modify
the standard dose schedule currently used in the delivery of this critical treatment.
Progress: This protocol closed to enrollment with one patient enrolled who continued to be
followed at MAMC during FY06.
366
_ Detail Summary Sheet _
Date: 30 Sep 06 Number: 205134 Status: Ongoing
Title: Clinical Trial and Retrospective Review to Determine the Sensitivity and Specificity of
Iminodiacetic Acid Scintigraphy for Fibrolamellar Carcinoma
Principal Investigator: CPT David C. Semerad, MC
Department: Radiology Facility: MAMC
Associate Investigator(s): LTC Antonio G. Balingit, MC; COL (Ret) Jerome L. Billingsley,
MD; LTC John D. Statler, MC
Start - Completion: Funding: Periodic Review:
1/11/2006 - Jul 2009 Nuclear Medicine 9/21/2006
Study Objective: To determine the sensitivity and specificity of iminodiacetic acid (IDA)
scinitgraphy for the detection of fibrolamellar carcinoma presenting as a solitary liver mass with a
central scar on CT examination.
Technical Approach: Patients at MAMC who have a solitary liver mass with a central scar on
CT will undergo IDA scintigraphy in addition to the standard diagnostic algorithm. It is estimated
that 12 patients will be studied at MAMC over a 4-year period. The study protocol will also be
submitted to IRBs at WRAMC and BAMC. A retrospective analysis of histologically-confirmed
FLCs with IDA scintigraphy findings will also be conducted at MAMC, WRAMC, and BAMC. The
goal number of total subjects is 80. The sole variable is radiopharmaceutical uptake of the lesion.
Data analysis is solely descriptive, i.e. establishing the sensitivity and specificity of IDA
scintigraphy for FLC.
Progress: This protocol remains open to enrollment, with no subjects enrolled.
367
Detail Summary Sheet
Date: 30 Sep 06 Number: 205051 Status: Ongoing
Title: Carotid Stenosis: Digital Subtraction Angiography, Magnetic Resonance Angiography, and
the Evolution of Preoperative Evaluation
Principal Investigator: LTC John D. Statler, MC
Department: Radiology Facility: MAMC
Associate Investigator(s): MAJ Joseph A. Ronsivalle, MC; CPT Christopher S. Johnson, MC;
CPT Vance Y. Sohn, MC; LTC Benjamin W. Starnes, MC; COL (Ret) Charles A. Andersen, MD;
Billinda Tatum, RN, CCRC; Leslie B. Schoneman, PA-C
Start - Completion: Funding: Periodic Review:
6/7/2005 - Mar 2007 DCI 2/28/2006
Study Objective: This study will serve as a validation that magnetic resonance angiography
(MRA) is no worse than catheter angiography in the evaluation of atherosclerotic disease of the
carotid arteries.
Technical Approach: All adult MAMC healthcare beneficiaries referred for carotid arteriography
(DSA) from vascular surgery clinic will be eligible for participation. If a patient agrees to be
enrolled in the study, he/she will be consented during the visit to the vascular surgery clinic. The
subject will be scheduled for DSA and MRA at the same time and will undergo both of these exams
in the most expeditious order possible. Once the exams have been completed, each subject's DSA
will be performed, reviewed and interpreted by one radiologist, and the MRA will be reviewed and
interpreted by the other radiologist. The radiologist interpreting the MRA will be blinded to the
results of the DSA, and vice-versa. Findings will be recorded on the data sheet. A general comment
will be made on the quality of each exam. The images will be evaluated for percent stenosis of the
common and internal carotid arteries using NASCET criteria (12) and measured by imaging
software. Findings will be made based on standardized imaging criteria. Findings which may alter
patient management (near occlusion, plaque ulceration, etc.) will be catalogued. At the conclusion
of the review of the MRA and DSA, the results for each subject will be compared. Each subject will
receive a grade with respect to the concordance of the two exams. A grade of "no difference"
indicates that MRA and DSA concurred with respect to percent stenosis (+ - 10%) of internal and
common carotid, and that there was no difference in detection of findings which would alter
patient management. A grade of "minor difference" indicates discordance between MRA and DSA
with respect to stenoses or associated findings, but that these discrepancies would not affect the
decision to operate or the operative approach. A grade of "major difference" indicates discordance
between MRA and DSA which would alter patient management or operative approach (discordant
stenosis category, associated findings which would alter surgical management).
Progress: This protocol remains open to enrollment with two patients enrolled. No adverse events
have been recorded. Subject accrual continues although the patient population from which to draw
is small.
368
Detail Summary Sheet
Date: 30 Sep 06 Number: 205024 Status: Ongoing
Title: Computed Tomography of the Abdomen Following Appendectomy
Principal Investigator: LTC John D. Statler, MC
Department: Radiology Facility: MAMC
Associate Investigator(s): MAJ Joseph A. Ronsivalle, MC; CPT Andrew E. Fong, MC; CPT
Brian C. Beldowicz, MC; CPT William T. Lewis, MC
Start - Completion: Funding: Periodic Review:
2/16/2005 - Feb 2006 DCI 12/13/2005
Study Objective: To determine the computed tomography (CT) findings of patients who have
recently undergone appendectomy.
Technical Approach: Adult male subjects will be recruited while in-hospital following their
appendectomy. Relevant labs (serum creatinine) and history (contrast allergy) will be reviewed,
and the subjects will be excluded from the study as indicated. Subjects meeting inclusion criteria
and wishing to participate in the study will be assigned a random patient number. The PI will
secure the code list. The subject will be given an appointment for CT scan of the abdomen on the
same day as his follow-up appointment in the surgery clinic. Subjects will arrive at the Dept of
Radiology, Computed Tomography section before their surgery clinic appointment. CT
technologists will verify the subject's eligibility to undergo the exam. The subject will ingest
approximately 1 1/2 liters of oral contrast. An intravenous line will be started. Following adequate
time (approximately 2 1/2 hrs) to opacify the small bowel, CT of the abdomen and pelvis with oral
and intravenous contrast will be obtained. The i.v. will be removed, and the subject will be
discharged to the surgical clinic. Total participation time should take approximately 3 hours.
Progress: This protocol remains open to enrollment with sixteen subjects enrolled. No adverse
events have occurred. One problem has been coaxing subjects to obtain final CT scan to complete
the study; four subjects did not undergo the follow up CT scan.
369
Detail Summary Sheets
Special Forces Group, Fort Lewis
370
Detail Summary Sheet
Date: 30 Sep 06 Number: 206106
Status: Ongoing
Title: 1st Special Forces Group (Airborne) Combat Trauma Management Procedures Training
for Special Forces Medical Personnel
Principal Investigator: COL Eric P. Wendt
Department: Special Forces
Facility: MAMC
Associate Investigator(s): CPT Lane A Hansen; Frank J. Newton
Start - Completion: Funding:
7/13/2005 - Jul 2008 1st Special Forces Group (Airborne)
Periodic Review:
N/A
Study Objective: Trauma is the leading cause of death among American ages 1-44. The purpose
of this training exercise is to teach critical trauma management and resuscitative tasks. This
exercise emulates, in part, the instruction in the Special Forces Medical Sergeant's/Advanced
Special Operations Combat Medic course. It is intenedd to teach lifesaving procedures under
simulated tactical scenarios which are stressful, challenging and austere.
Technical Approach: Combat management training is conducted in a simulated battlefield on a
pultiply wounded patient. The student must accurately acfcess the patient, resuscitate him, and
then treat the wounds in a timely manner. The student will perform a preliminary physical
examination of the animal subject and determine that the subject can safely tolerate the
physiologic demands of general anesthesia, wounding and resuscitation. The animal is placed
under general anesthesia using intravenous anesthetic agents. When the animal has reached the
appropriate level of anethesia, an instructor inflicts simulated battlefield injuries. The animal is
transported to a Combat Trauma Management scenario for resuscitative procedures. The student
is immediately summoned and begins an exercise comprised of primary and secondary
assessments, resuscitation, wound treatment and casualty evacuation. The successful student will
recognize life threatening conditions and initiate immediate and appropriat medical treatment.
The protocols is also used to sustain medical skills of those who have already graduated from the
JSOMTC or it's predecessor, the "Med Lab." This pecifically applies to the Special Forces Medical
Sergeant's Advanced Non-Commissioned Officer's Cours Combat Trauma Management Procedures
Training or the Special Operations Forces Medical Skills Sustainment Program.
Progress: No goats have yet been utilized for this protocol.
371
Detail Summary Sheet
Date: 30 Sep 06 Number: 206018
Status: Ongoing
Title: 1st Special Forces Group (Airborne) Instructing Combat Trauma Management to Trainees
Principal Investigator: COL Eric P. Wendt
Department: Special Forces
Facility: MAMC
Associate Investigator(s): CPT Lane A Hansen; Frank J. Newton
Start - Completion: Funding:
7/13/2005 - Jul 2008 1st Special Forces Group (Airborne)
Periodic Review:
N/A
Study Objective: To allow SOMO instructors to train SOMNCOs in methods of teaching selected
volunteers to perform lifesaving medical procedures and to recognize the indication for these
procedures.
Technical Approach: CTM training is conducted in a simulated battlefield on a multiple
wounded patient. The medic acting as Student-Trainer must teach accurate assessment and
resuscitation of the patient. The student-Trainer must instruct the trainees in how to treat the
wounds in a timely manner. The Student-Trainer will begin by demonstrating to the Instructor-
Trainer how to perform a preliminary physical examination of the animal subject in order to
determine whether the animal can safely tolerate the physiologic demands of general anesthesia,
wounding, and resuscitation. The animal is then placed under general anesthesia by the Student-
Trainer (under supervision of the Attending Veterinarian) using intravenous and/or inhalant
anesthetic agents. When the animal has reached the appropriate level of anesthesia, the Student-
Trainer inflicts simulated battlefield injuries. The animal is transported to a Combat Trauma
Management scenario for resuscitative procedures.
The Trainees/Volunteers will immediately be summoned with the battlefield call of "MEDIC",
"Corpsman" or a regionally appropriate foreign language equivalent title, and will then begin an
exercise comprising primary and secondary assessments, resuscitation, wound treatment, and
casualty evacuation. The Special Operations Medic acting as the Student-Trainer will be graded
on how successfully he teaches, coaches and mentors the Volunteers in recognizing life-threatening
conditions and in initiating immediate and appropriate medical treatment.
Progress: Fifteen animals were utilized to train 9 Trainers and 72 Students during FY06.
372
Detail Summary Sheets
General Surgery Service, Department of
Surgery
373
Detail Summary Sheet
Date: 30 Sep 06 Number: 206032
Status: Ongoing
Title: Colonic Ischemia Following Abdominal Aortic Aneurysm Repair--
Approaches
Principal Investigator: CPT Zachary M. Arthurs, MC
Open vs. Endovascular
Department: Surgery/General Surgery
Facility: MAMC
Associate Investigator(s): MAJ Scott R. Steele, MC; LTC Matthew J. Martin, MC; MAJ Philip
S. Mullenix, MC; LTC Benjamin W. Starnes, MC; COL (Ret) Charles A. Andersen, MD; COL
Kenneth S. Azarow, MC
Start - Completion: Funding:
12/14/2005 - Dec 2006 DCI
Periodic Review:
N/A
Study Objective: To determine if there are any differences in colonic ischemia complications
following abdominal aortic aneurysm repair using an open versus an endovascular approach and
determine any peri-operative factors which may contribute to that difference.
Technical Approach: This is a retrospective review comparing a consecutive series of
endovascular repairs for abdominal aortic aneurysms. A chart review of all cases of the
endovascular approach will be performed and results compared to historical controls of the open
approach. Open patients will be consecutive patients coming from the time period just preceding
the startup of the endovascular approach. ORMA will be used to generate the patient names for
each of the two methods to perform the chart review.
Progress: A review of just over 70 EVAR cases identified that only one colorectal complication
occurred with those procedures. Data collection continues with all open cases. Investigators plan to
seek collaboration with other military medical facilities and extend this protocol as a multisite
study.
374
Detail Summary Sheet
Date: 30 Sep 06 Number: 206123 Status: Ongoing
Title: Renovascular Hypertension: A Retrospective Analysis of Renal Artery Stenting Outcomes
Principal Investigator: CPT Zachary M. Arthurs, MC
Department: Surgery/General Surgery Facility: MAMC
Associate Investigator(s): CPT Daniel G. Cuadrado, MC; CPT Vance Y. Sohn, MC; COL (Ret)
Charles A. Andersen, MD; LTC Benjamin W. Starnes, MC
Start - Completion: Funding: Periodic Review:
9/13/2006 - Dec 2007 DCI N/A
Study Objective: 1. To establish the impact of renal artery stenting on patients hypertension
control and on their renal function.
2. To determine the natural history of patients that have not been treated with stenting of the
renal arteries.
Technical Approach: To perform a retrospective review of inpatient and outpatient records for
patients that were presented at a Multidisciplinary Renovascular Conference, which included
nephrologists, interventional radiologists, and vascular surgeons. Patients with atherosclerotic
renal artery disease are to be included between January 2001 and June 2006. Patients presented
at this conference were referred by nephrologists for multiple medication hypertension, worsening
renal function, or congestive heart failure. The multidisciplinary team evaluated each patient for
potential renal artery stenting, and as a result there was a cohort of patients that were followed
with medical management. Reasons patients were not offered stenting include: inadequate anti¬
hypertensive regimen, poor patient compliance, acute medical conditions, resistive indice >0.80,
and lesions that were <70% stenosis. A retrospective chart analysis will be performed of inpatient
and outpatient up records. The patients that were not offered stenting will be used as a
comparison against the population that underwent stenting. While not an adequate control since
these patients were selected by the conference, they will provide a comparison for the natural
history of worsening renovascular disease. Initial screening of the renal vascular bed is performed
with duplex ultrasound criteria, and if the study was noncontributory, magnetic resonance
angiography (MRA) or computed tomographic angiography (CTA) was performed as a confirmatory
test.
Progress: This minimal risk protocol received initial approval by the Expedited Review
Committee, effective 20 September 2006.
375
Detail Summary Sheet
Date: 30 Sep 06 Number: 203090 Status: Ongoing
Title: The Association Of Elevated C-Reactive Protein With Presence And Degree Of Carotid
Stenosis
Principal Investigator: CPT Zachary M. Arthurs, MC
Department: Surgery/General Surgery Facility: MAMC
Associate Investigator(s): MAJ Philip S. Mullenix, MC; COL (Ret) Charles A. Andersen, MD;
Leslie B. Schoneman, PA-C; CPT Garth S. Herbert, MC; CPT Craig S. See, MC; LTC Benjamin
W. Starnes, MC; CPT Katharine E. Wolcott, MC; CPT Daniel G. Cuadrado, MC; MAJ Allen D.
Rubin, MC
Start - Completion: Funding: Periodic Review:
7/1/2003 - Dec 2005 DCI 8/28/2006
Study Objective: Evaluate the association between serum CRP levels and the presence and
degree of carotid stenosis.
Technical Approach: This is a prospective observational concurrent cohort study evaluating the
potential relationship between serum C-reactive protein levels and the presence and degree of
carotid stenosis. It involves two study arms, a cohort with carotid stenosis, and one without, as
defined by bilateral carotid duplex ultrasound. The study involves two phases. Phase I will (1)
compare the measured initial CRP means between the two cohorts, and (2) correlate the amount of
elevation of CRP with the measured degree of carotid stenosis. Phase II is a longitudinal study
designed to stratify increased risk of progression of carotid disease or adverse neurologic outcomes
using odds rations generated from measured CRP quartile means.
Progress: This protocol closed to enrollment with 361 subjects enrolled. Of that number 72 will
complete their three-year involvement by December 2006 and the protocol will continue until the
remaining subjects reach their three-year study participation.
376
Detail Summary Sheet
Date: 30 Sep 06 Number: 203107 Status: Completed
Title: A Multicenter, Open-Label, Randomized Study To Compare The Safety And Efficacy Of
Once Daily Levofloxacin Along With Once Daily Metronidazole Versus Piperacillin / Tazobactam
In The Treatment Of Complicated Appendicitis, Protocol CAPSS-151
Principal Investigator: COL Kenneth S. Azarow, MC
Department: Surgery/General Surgery Facility: MAMC
Associate Investigator(s): MAJ Alec C. Beekley, MC; MAJ James A. Sebesta, MC; CPT Amy
L. Young, DO; LTC Robert M. Rush, MC; Margaret I. Voelker, RN, CRC; CPT Troy P.
Houseworth, MC; CPT Rebecca M. McGuigan, MC; CPT Neil R. Stockmaster, MC; CPT Craig S.
See, MC; CPT James C. Nunley, MC
Start - Completion: Funding: Periodic Review:
11/18/2003 - Oct 2006 Ortho-McNeil Pharmaceutical via Henry M. 8/10/2006
Jackson Foundation
Study Objective: Primary: To determine the safety and efficacy of the treatment regimen
containing levofloxacin and metronidazole compared to the regimen of Piperacillin/Tazobactam in
the treatment of complicated appendicitis. Secondary Objectives: To assess clinical response at
Post-therapy visit among microbiologically evaluable patients; to assess clinical response at post
study phone contact among clinically and microbiologically evaluable patients; To assess
microbiologic response at Post- therapy visit by patient and by pathogen(s) isolated at study entry
among microbiologically evaluable patients; to compare total costs associated with care (average
length of hospital stay, cost of drugs, administration costs, time to oral switch, and duration of
treatment) for each treatment group.
Technical Approach: This is a multicenter, open-label, randomized study comparing two
treatments for complicated appendicitis in male and female patients 18 years or older.
Approximately 1500 subjects will be enrolled in the trial for the goal of 420 evaluable patients. At
MAMC, 10-20 subjects may be enrolled over 2-3 years. Patients suspected of having complicated
appendicitis and requiring surgery will be screened for enrollment by study investigators of the
MAMC General Surgery Service. Patients meeting eligibility criteria will be randomized in 1:1
ratio to two treatment groups. The first antibiotic regimen dose is given prior to surgery. Group I
will receive the drug combination under study, levofloxacin 750 mg, IV, every 24 hours followed by
metronidazole 1500 mg, IV, every 24 hours. After at least 48 hours of IV administration, patients
may be switched to oral levofloxacin 750 mg every 24 hours and metronidazole 1500 mg by mouth
every 24 hours. The oral antibiotics will be continued for a total of 4 - 14 days of therapy. Group 2
will receive the comparator regimen, Piperacillin/Tazobactam 3.375 grams, IV, every 6 hours. The
first dose is given before surgery. Patients may be switched after 48 hours of IV therapy to oral
amoxicillin/clavulanate 875/125 every 12 hours for a total of 4 - 14 days.
Patients who are found at surgery to have appendicitis complicated by rupture and intra¬
abdominal/peritoneal infection will be continued in the study. Fluids for culture and sensitivity
testing will be obtained intraoperatively and sent to MAMC clinical laboratory and the study
central laboratory. Patients who do not have complicated appendicitis confirmed will be
discontinued from the study to receive interventions per clinical standards.
Patients will return after hospital discharge for a follow-up assessment at the end of treatment
and a telephone contact will be done for data collection at 30 days after end of treatment.
Assessments performed during hospitalization and at follow up include evaluation of clinical
symptoms and signs, adverse events, vital signs, concomitant medications, hematology and serum
chemistry assays. Patients with baseline positive blood cultures will receive appropriate follow up
377
blood cultures during and after therapy. Study design includes procedures for unscheduled follow
up in the case of postoperative wound infection or an intra- abdominal abscess. A modified intent to
treat population will be utilized including all randomized patients who receive at least one dose of
study drug and are found to have complicated appendicitis. Clinical efficacy will be evaluated by
clinical and microbiological response. Hospital resource use will be evaluated by length of stay and
length of antibiotic treatment. Safety analysis will examine incidence, severity, types of adverse
events, changes in physical findings and abnormalities in vital signs and laboratory values. An
interim analysis will be performed.
Progress: This protocol completed all study related activity during FY05 and was reported
completed at MAMC in September 2006, with thirteen patients consented/completed study visits
and four patients documented as lost to follow-up.
378
Detail Summary Sheet
Date: 30 Sep 06 Number: 204013
Status: Completed
Title: Abdominal Wall Defects: Does the Intraabdominal Pressure Affect Outcome?
Principal Investigator: COL Kenneth S. Azarow, MC
Department: Surgery/General Surgery
Facility: MAMC
Associate Investigator(s): CPT Rebecca M. McGuigan, MC
Start - Completion: Funding:
11/12/2003 - Nov 2003 DCI
Periodic Review:
11/22/2005
Study Objective: To retrospectively analyze neonates with abdominal wall defects at Madigan
since 1997 in order to determine whether splanchnic perfusion pressure affects and/or is predictive
patient outcome.
Technical Approach: This study is a retrospective chart review of all patients treated at
Madigan Army Medical Center with congenital abdominal wall defects diagnosed at birth. The
effect of intragastric and intraabdominal pressure and "splanchnic perfusion pressure" on the
incidence of complications and overall outcome will be analyzed.
Progress: This protocol was reported completed during FY06. A paper was published in Journal of
Pediatric Surgery adding MAMC results to those of Children's Hospital Seattle and Children's
Hospital of Illinois, Peoria. "McGuigan, Mullenix, Vegunta, Peal, Sawin, and Azarow. Splanchnic
Perfusion Pressure: a better predictor of safe primary closure than intraabdominal pressure in
neonatal gastroschisis." J Pediatr Surg 2006. 41: 901-904.
379
Detail Summary Sheet
Date: 30 Sep 06 Number: 204058 Status: Ongoing
Title: Advanced/Combat Trauma Management Training Using Animal Models (Domestic
Goat/Capra hircus, Pig/Sus scrofa)
Principal Investigator: MAJ Alec C. Beekley, MC
Department: Surgery/General Surgery Facility: MAMC
Associate Investigator(s): MAJ James A. Sebesta, MC; LTC Benjamin W. Starnes, MC
Start - Completion: Funding: Periodic Review:
3/10/2004 - Mar 2007 Units via MOU 3/8/2006
Study Objective: This protocol is intended to facilitate advanced and combat trauma
management training of federally affiliated (e.g. DoD AC/RC, VA) physicians and ancillary medical
personnel (e.g. nurse, physician's assistant, medic, medical/surgical technician, etc.).
Technical Approach: The protocol supports three levels of trauma management training, as
follows: 1) Combat Relevant Trauma Management training for surgeons (CTM-S), focusing on
preservation of life, limb, critical organ function, and casualty stabilization prior to medical
evacuation for definitive care. 2) Combat-relevant Trauma Management training for physicians
(CTM-P), focusing on preservation of life, limb, critical organ function, and casualty stabilization
prior to medical evacuation for definitive care. 3) Combat-relevant Trauma Management training
for ancillary medical personnel (CTM-NP), focusing on "hands-on" training of mission/ duty-related
trauma intervention procedures. Training associated with this protocol will utilize both inanimate
(e.g. mannequin, cadaver, Simman, etc.) and live, anesthetized animal models. Whenever feasible,
inanimate models will be used in place of live animals. Animal species used for this protocol will
include goat and swine. The number of animals required is based on deployment of troops: Swine -
Three to five personnel per animal, estimated that not more than 50 would be used per year. Goat
- Three to five personnel per animal estimated that not more than 250 would be used per year.
Progress: Twelve labs were held during FY 06, providing predeployment combat casualty training
for 194 medics and 28 3rd year Madigan residents, using 46 animal models. Protocol will continue
with labs planned for training 200 medics and 30 3rd year Madigan residents in FY 2007.
380
Detail Summary Sheet
Date: 30 Sep 06 Number: 205075 Status: Ongoing
Title: Operation Iraqi Freedom Combat Trauma Database from the 31st Combat Support
Hospital, Baghdad, Iraq
Principal Investigator: MAJ Alec C. Beekley, MC
Department: Surgery/General Surgery Facility: MAMC
Associate Investigator(s): MAJ James A. Sebesta, MC; LTC Tommy A. Brown, MC; COL (Ret)
Charles A. Andersen, MD; COL Kenneth S. Azarow, MC; MAJ Philip S. Mullenix, MC; CPT
Zachary M. Arthurs, MC; CPT Randy J. Kjorstad, MC; CPT Troy P. Houseworth, MC; CPT
Rebecca M. McGuigan, MC; CPT Daniel G. Cuadrado, MC
Start - Completion: Funding: Periodic Review:
5/6/2005 - Jan 2010 DCI 4/20/2006
Study Objective: To retrospectively review the recorded combat trauma, burn, pediatric,
vascular, elective, and humanitarian surgical activities collected at the 31st Combat Support
Hospital, Baghdad, Iraq between 1 Jan 04 and 31 Dec 04 that was recorded in an existing, secure,
and confidential database for purposes of (1) continuous quality analysis/improvement of military
surgical care in combat and (2) academic publication and presentation.
Technical Approach: Retrospective database (spreadsheet) review. Specific study questions
(spreadsheet queries) will be submitted as specific addendums. Examples of typical study
questions of interest might include (descriptive data analysis of existing spreadsheet only):
Incidence of military admissions compared to civilian admissions at a large CSH. Primary and
secondary surgical procedures performed compared between various patient subsets. Percentage of
patients requiring ICU admissions compared between various patient subsets. Mortality rate of
patients compared between various patient subsets. Length of ICU and Hospital stay compared
between various patient subsets. Admission laboratory data to include vitals, Glasgow coma score,
complete blood count, arterial blood gas with base deficit, and blood products administered.
Distribution of primary and secondary cause of injury compared between various patient subsets.
Incidence of damage control operations and operative times compared between various patient
subsets. Injury severity scores compared between various patient subsets. Cause of death
compared between various patient subsets. Proportion of patients that received level one or level
two care as compared between various patient subsets.
Procedures: Dr. Beekley (PI) and Dr. Beekley alone will create code list for patient name/SSN. He
will then permanently delete PHI (name/SSN/PHI) field columns from Excel spreadsheet and
replace with code list number. Then he will permanently destroy all records of name/SSN/PHI
leaving only the code list number. Even the PI will not have PHI after that point, and none of the
AI's will ever see PHI. Decide on a specific study question of interest for database query. Submit
addendum to this protocol to MAMC IRB with specific question and variables to be analyzed. Cut
and paste pertinent study data from secure de-identified computerized Excel spreadsheet file into
new spreadsheet specific to that problem (delete irrelevant fields, calculate new variables from
existing data). Maintain the new spreadsheet in same secure, de-identified manner using existing
code list system.
Analyze data. Due to the nature of the database and fields available, these statistical analyses
employed will be straightforward, descriptive, and observational in nature, in general designed to
compare various subset cohorts identified within the total data set. Report and present data in
entirely de-identified fashion (no names, patient numbers, patient specific data or identifiable
injury pattern, etc - typical chart review reporting). Destroy code list specific to that study question
and destroy all hard copies if any.
381
Progress: Institute of Surgical Research recently (as of mid-October 2006) completed accurate
Injury Severity Scores for the patients in the 31st CSH database. Analysis of this data is ongoing.
Planned comparison to outcomes from Trisat database in San Antonio is expected to start in next
1-2 months.
382
Detail Summary Sheet
Date: 30 Sep 06 Number: 204106 Status: Completed
Title: A Multicenter, Double-blind, Randomized, Phase 3 Study to Compare the Safety and
Efficacy of Intravenous Doripenem with that of Meropenem in Complicated Intra-abdominal
Infections
Principal Investigator: ETC Tommy A. Brown, MC
Department: Surgery/General Surgery Facility: MAMC
Associate Investigator(s): COL Kenneth S. Azarow, MC; CPT Farah A. Husain, MC; CPT
Garth S. Herbert, MC; CPT Kathleen M. Goings, MC; MAJ Scott R. Steele, MC; MAJ Philip S.
Mullenix, MC; CPT Garth S. Herbert, MC
Start - Completion: Funding: Periodic Review:
11/5/2004 - Dec 2005 Peninsula Pharmaceuticals, Inc via The 7/27/2005
Geneva Foundation
Study Objective: Primary objective: to compare the clinical response of Doripenem vs.
Meropenem in hospitalized subjects with complicated intra-abdominal infections (cIAI) at the test-
of-cure visit (TOC). The TOC visit is the late follow-up visit (4 to 6 weeks after the completion of
therapy). Secondary objectives: (1) to compare the microbiological response of doripenem vs.
Meropenem at the test-of-cure visit (4 to 6 weeks post-treatment), (2) to compare the clinical
response of doripenem vs. Meropenem at the early follow-up visit (1 to 2 weeks post-treatment), (3)
to compare the microbiological response of doripenem vs. Meropenem at the early follow-up visit (1
to 2 weeks post treatment), and (4) to compare the safety of IV doripenem with that of Meropenem.
Technical Approach: Subjects will be stratified before randomization based on primary sites of
infection complicated appendicitis versus diagnosis of other sites of intra-abdominal infections and
severity of illness (APACHE II score less than or equal to 10 or more than 10. Subjects will be
assigned to study drug regimen using a computerized randomization to minimize bias. Except for
the responsible study site pharmacist or designee, all study participants will be blinded to the IV
dosing regimen of all subjects. Aerobic and anaerobic specimens for culture will be collected at the
time of the initial procedure (within 24 hours of enrollment). Aerobic specimens will be cultured
and quantified in the local laboratory. The isolate(s) will be sent to a central, reference laboratory
for validation of identification and susceptibility testing. All anaerobic specimens of infected fluid
or tissue will be sent in transport medium directly to a central, reference laboratory for anaerobic
isolation, identification, and susceptibility testing.
After at least 6 doses (approximately 48 hours) of IV study drug therapy administered while
subjects are hospitalized, subjects may be discharged if arrangements are made for continued IV
administration of study drug and the collection of all required study assessments. Subjects may be
switched to oral amoxicillin/clavulanate tablets (875mg / 125mg twice daily) after 9 or more doses
of IV study drug therapy if all of the following criteria are met: (1) Body temperature and WBC
count are decreasing compared to Day 1 pre-dose. (2) Signs and/or symptoms of cIAI are absent or
improved compared to Day 1 pre-dose and (3) Bowel function has returned. There should be at
least 8 hours between the last dose of IV study drug and first dose of oral amoxicillin/clavulanate.
After randomization, patients will receive Doripenem injection 500 mg 60-minute IV infusions q 8
hours or Meropenem 1 gm by IV bolus over 3-5 minutes q 8 hours. Addition of open-label
vancomycin is permitted if Enterococcus or methicillin-resistant Staphylococcus aureus is one of
the pathogens isolated. This study will last approximately 6 to 8 weeks. Screening may occur up to
24 hours prior to the infusion of the first dose of study drug. The total days of IV and oral study
drug therapy will be 5-14 days. An early follow-up visit will be conducted 7-14 days after the final
dose of study drug is administered. The TOC visit will be 28-42 days (4-6 weeks) after the final
dose of study drug.
383
Clinical outcome assessment will be made at the early follow-up visit and at the TOC visit.
Clinical response will be classified as cure, failure, or indeterminate based on clinical outcome. A
favorable clinical response is "cure". Once a subject has an "unfavorable" response at any clinical
assessment, the subject will be counted as having an "unfavorable" response at all subsequent
time points.
Progress: This protocol was reported completed in June 2006, with six subjects enrolled; four
completed, two dropped from study, and two internal serious adverse events reported.
384
Detail Summary Sheet
Date: 30 Sep 06 Number: 206015 Status: Ongoing
Title: A Prospective Randomized Study Comparing Sentinel Lymph Node (SLN) Evaluation
with Standard Pathological Evaluation for the Staging of Colon Carcinoma
Principal Investigator: ETC Tommy A. Brown, MC
Department: Surgery/General Surgery Facility: MAMC
Associate Investigator(s): LTC Gregory P. Fitzharris, MC; MAJ James A. Sebesta, MC; MAJ
Alec C. Beekley, MC; LTC Robert M. Rush, MC
Start - Completion: Funding: Periodic Review:
6/9/2006 - Oct 2010 DCI 11/21/2006
Study Objective: The objective of this trial is to define the rate of upstaging of colon carcinoma
lymph node metastasis with sentinel lymph node (SLN) mapping.
Technical Approach: Male and female military healthcare beneficiaries over the age of 18 years
presenting at the General Surgery Clinic with the diagnosis of biopsy-proven, primary, non¬
metastatic (Clinical Stage I, II or III) colon carcinoma will be enrolled. Subjects with colonic masses
clinically consistent with colon cancer and eventually confirmed by pathology, will also be enrolled.
A total of 150 patients will be enrolled; up to 20 patients per year are expected to be enrolled at
MAMC. A complete history and physical examination including demographic data, co-morbid
conditions, past surgical history, clinical tumor staging, American Society of Anesthesiologists
classification, height and weight will be performed within one month before surgery. Pre-operative
evaluation will consist of complete blood count (CBC), coagulation profile (PT/PTT), screening
profile including: electrolytes, blood urea nitrogen, creatinine, pulmonary function testing, chest
radiography and electrocardiogram (at the discretion of the attending surgeon). Pre-operative
clinical staging will be conducted according to MAMC current standard of care and will include
colonoscopy and serum carcinoembryonic antigen (CEA).
Subjects randomized to the standard histopathology arm will undergo a standard surgical
resection of the colon cancer. The entire surgical specimen (colon and mesentery) will be sent to
the pathologist for standard histopathological evaluation and staging of the cancer using
conventional paraffin embedding, sectioning and hematoxylin and eosin staining (H&E) and
microscopy. Subjects randomized to the SLN arm of the trial will undergo standard surgical
resection of the colon cancer including the normal wedge of mesentery containing the draining
lymphatics. Immediately following resection the surgical specimen will be stained. The
investigator will dissect all blue nodes from the mesentery and submit them to pathology as
separately labeled specimens (SLNs). The remaining resected colon with attached mesentery will
then be sent fixed in formalin for standard histopathological evaluation of non-SLNs, as per
standard of care protocol. The SLN pathology results will be made available to both the subject
and the subject's physician. Subject participation will conclude with the surgical procedure. No
follow-up is required for this clinical trial.
Progress: This protocol remains open to patient entry, with two patients enrolled during FY06.
385
Detail Summary Sheet
Date: 30 Sep 06 Number: 205074 Status: Completed
Title: A Randomized, Double-Blind Study of GT267-004 Versus Vancomycin, and GT267-004
Versus Metronidazole, in Patients with C. Difficile-Associated Diarrhea; Protocol GD3- 170-301
Principal Investigator: LTC Tommy A. Brown, MC
Department: Surgery/General Surgery Facility: MAMC
Associate Investigator(s): COL Kenneth S. Azarow, MC; MAJ James A. Sebesta, MC; MAJ
Alec C. Beekley, MC; Margaret I. Voelker, RN, CRC
Start - Completion: Funding: Periodic Review:
8/10/2005 - Jun 2007 Genzyme Corporation via Henry M. Jackson 4/25/2006
Foundation
Study Objective: (1) To compare the safety tolerability of GT267-004 versus vancomycin, and
GT267-004 versus metronidazole, inpatients with Clostridium difficile-associated diarrhea
(CDAD). (2) To compare the effect of GT267-004 versus vancomycin, and GT267-004 versus
vancomycin, and GT267-004 versus metronidazole, on the resolution of CDAD. (3) To compare the
effect of GT267-004 versus vancomycin, and GT267-004 versus metronidazole, on the rate CDAD
recurrence during the follow-up period. (4) To compare the safety, tolerability and efficacy of
vancomycin versus metronidazole for resolution of CDAD and recurrence rates.
Technical Approach: This is a Phase III, double-blind study to compare the safety and efficacy of
GT267-004 versus Vancomycin and GT267-004 versus Metronidazole for the treatment of
Clostridium difficile-associated diarrhea (CDAD). The study consists of a two week treatment
period, during which patients will receive GT267-004, Vancomycin or metronidazole per
randomization. The treatment period is followed by a 4 week follow-up period. The total study
duration is 6 weeks. Patients randomized to the vancomycin dose group will receive a 10 day
course given in combination with a 14 day course of GT267-004 placebo. Patients randomized to
the metronidazole dose group will be given a 10 day course with a 14 day course of GT267-004
placebo. Patients randomized to the GT267-004 dose group will be given 14 days of in combination
with 10 days of vancomycin or metronidazole placebo. During treatment, stool counts and
consistency will be monitored daily by the study staff, either in person for inpatients or by phone
for outpatients. Lab samples for serum potassium will be collected on days 4, 8 and 12 (+ 2 days).
A complete exam with safety labs will be collected on Days 8 and 15. Recurrence rates will be
followed for 4 additional weeks up to week 6 and will follow procedures outlined in section 12.6 of
the protocol pages 28-29. Non-responders will have study treatment discontinued and will begin c-
difficile treatment at needed.
Progress: A study site close out visit was conducted in September 2006. A total of 9 patients were
screened for this protocol; only two were consented, randomized and enrolled. One subject
completed the entire course of study treatment and follow-up. The other subject withdrew
participation due to a serious adverse event, dehydration, which the PI deemed as anticipated for a
person diagnosed with C. Difficile-associated diarrhea.
386
Detail Summary Sheet
Date: 30 Sep 06 Number: 205096 Status: Completed
Title: ACOSOG Z4031, Use of Proteomic Analysis of Serum Samples for Detection of Non-Small
Cell Lung Cancer
Principal Investigator: LTC Tommy A. Brown, MC
Department: Surgery/General Surgery Facility: MAMC
Associate Investigator(s): LTC Gregory P. Fitzharris, MC; MAJ James A. Sebesta, MC; MAJ
Alec C. Beekley, MC; LTC Robert M. Rush, MC
Start - Completion: Funding: Periodic Review:
3/3/2006 - Jul 2010 ACOSOG via Henry M. Jackson Foundation N/A
Study Objective: (1) To determine prospectively whether the serum proteomic profile can predict
the presence of primary NSCLC in patients with suspicious lung lesions who are candidates for
lung resection. (2) To correlate the serum proteomic profile with pathologic nodal status and
histopathologic features of primary lung cancer in patients with NSCLC undergoing lung
resection. (3) To correlate the initial serum proteomic profile with overall and cancer-specific
survival in patients with NSCLC undergoing lung resection. (4) To correlate the follow-up serum
proteomic profile with overall and cancer-specific survival in patients with NSCLC undergoing
lung resection. (5) To correlate changes in the proteomic profile (pre- operative to post-operative)
with overall and cancer- specific survival in patients with NSCLC undergoing lung resection. (6) To
acquire biospecimens prospectively and determine if novel molecular strategies can predict the
presence of lung cancer and/or the biologic behavior of an individual cancer.
Technical Approach: This study will collect pre and post surgical serum samples on about 1200
patients having surgical resection for suspected non-small cell carcinoma. Patients who are found
to have a malignant tumor will also have tissue samples submitted. Protein profiling will be done
on samples to search for diagnostic and prognostic indicators. Patients who are eligible to
participate will have data collected on in the form of history and physical exam, radiologic reports,
and operative reports. Patients found to have benign tumors will be followed yearly for 2 years for
survival data. Patients found to have malignant tumors will be followed annually for 5 years for
survival data. This study is to prospectively determine whether the serum proteomic profile can
predict the presence of primary lung cancer in patients with suspicious lung lesions who plan to
undergo a lung resection for diagnosis or treatment. For statistical modeling, the estimated
number of patients needed is: 300 patients with benign diagnosis, 350 patients with
adenocarcinoma, 200 patients with squamous cell carcinoma, and 150 patients with other types of
malignant tumors. Patients with mixed histology will be assigned to the group of the predominant
cell type. In order to have at least 300 patients with a benign pathologic diagnosis, a sample size
recalculation will be conducted when about 800 patients are entered into the study, to increase the
sample size by up to 20%. With an expected annual accrual of 500 patients, it will take
approximately 2 years for total accrual. The patients will be followed for an additional 2 or 5 years
after the completion of accrual for the survival endpoint, depending on final diagnosis.
Progress: Accrual goals were met as of 17 April 2006, and the protocol was reported completed
with no subjects enrolled at MAMC.
387
Detail Summary Sheet
Date: 30 Sep 06 Number: 206101 Status: Ongoing
Title: ACOSOG Z6041: A Phase II Trial of Neoadjuvant Chemoradiation and Local Excision for
uT2uN0 Rectal Cancer
Principal Investigator: ETC Tommy A. Brown, MC
Department: Surgery/General Surgery Facility: MAMC
Associate Investigator(s): LTC William B. Reece, MC; MAJ Joseph P. Brooks, MC; MAJ
Angela G. Mysliwiec, MC; MAJ Jasmine T. Daniels, MC; LTC David E. McCune, MC
Start - Completion: Funding: Periodic Review:
10/10/2006 - Aug 2010 ACOSOG via Henry M. Jackson Foundation N/A
Study Objective: Objectives: To determine the rate of disease-free survival at 3 years in
ultrasound-staged uT2uN0 rectal cancer patients treated with chemoradiation (CRT) followed by
local excision (LE). To determine the rate of respectability with negative margins, procedure-
specific morbidity and mortality, and quality of life in ultrasound- staged Ut2uN0 rectal cancer
treated with neoadjuvant CRT followed by LE. To determine the feasibility of using molecular
studies to assess surgical resection margins and tumor response to neoadjuvant CRT.
Technical Approach: This is a Phase II study of preoperative chemoradiation in patients with
uT2uN0 rectal cancer. Patients will be identified and consented in the Surgical Oncology
department. Prior to registration they will have a physical exam; lab work, scans and quality of
life questionnaires (QOL). Eligible patients will be registered and begin treatment. Prior to
chemoradiation patients will have biopsy samples collected and tumor tattooing to mark tumor
measurement. Chemotherapy will be given as oral capecitabine on days 1-14 and 22-28, and IV
oxaliplatin on days 1, 8, 22, and 29. Radiation therapy will be given concurrently according to
standard therapy, five days a week, for weeks 1 through 5. During chemoradiation, patients will be
followed with weekly exams, adverse advent assessment and lab tests. At week 12, patients will
have local excision of remaining tumor, including collection of tissue specimens for correlative
studies, and measurement of tattoo marks to mark response to treatment. Follow up will take
place at Month 4 and every 4 months through Year 3. Patients will be followed every 6 months
through Year 5. Follow-up procedures will include proctoscopy and CEA, endorectal ultrasound,
and QOL.
Progress: This protocol remains open to patient entry, with no patients enrolled.
388
Detail Summary Sheet
Date: 30 Sep 06 Number: 205098 Status: Terminated
Title: ACOSOG Z9031, A Phase III Randomized Study of Preoperative Radiation Plus Surgery
Versus Surgery Alone for Patients with Retroperitoneal Sarcomas (RPS)
Principal Investigator: LTC Tommy A. Brown, MC
Department: Surgery/General Surgery Facility: MAMC
Associate Investigator(s): LTC William B. Reece, MC; MAJ James A. Sebesta, MC; MAJ Alec
C. Beekley, MC; LTC Robert M. Rush, MC; LTC John B. Halligan, MC
Start - Completion: Funding: Periodic Review:
1/9/2006 - Jul 2010 ACOSOG via Henry M. Jackson Foundation N/A
Study Objective: To evaluate whether preoperative radiotherapy of 45.0-50.4 Gy plus surgery
improves the PFS compared to surgery alone in patients with primary RPS. Secondary Objectives:
(1) To assess the toxicity and complications associated with preoperative radiotherapy and
surgery. (2) To assess whether preoperative radiation increases the rates of microscopically
complete surgical resection (R0). (3) To assess whether preoperative radiation increases the overall
survival rate of patients with RPS.
Technical Approach: Up to 370 patients with primary RPS will be enrolled to this study, with
approximately 2 patients per year enrolled at MAMC. Patients in the surgical arm will have a
history and physical, surgical consult, scans including chest x-ray, CT, and IV pyelogram, and lab
tests including CBC, Chemistry, LFT's and urine or serum pregnancy test for women of child
bearing potential. Post surgery, patients will be followed with physical exam, chest x-ray and CT
scans at Month 4, every 6 months afterwards unit Year 5, then annually until 10 years or death,
whichever comes first. Patients on the radiation therapy arm will have the same procedures, and
in addition will receive radiation therapy once a day, 5 days a week, for five and a half weeks.
Patients will also be offered participation in the specimen correlative study. Blood samples will be
collected prior to radiation therapy, prior to surgery, post surgery, at yearly follow-up and at
recurrence. Tissue samples will be taken from tumor already removed at time of surgery.
The primary analysis will be by randomized arm (intent-to-treat). PFS and overall survival (OS)
data will be analyzed using the log-rank test and Cox regression. Toxicity (grade 2 or lower vs. 3 or
higher), complications and resectability (complete resection vs. others) data will be analyzed using
the chi-squared test and logistic regression method. The multivariate data analyses will compare
the two arms adjusting for the stratification factors and some additional covariates such as age (65
years old or younger vs. 65+ years), macroscopically complete resection (yes vs. no), microscopic
surgical margin status, and anatomic location (pelvic epicenter vs. non-pelvic). For a direct
comparison of our results with those from other studies, subset analyses will be conducted for: (1)
the subset of patients that undergo macroscopically complete tumor resection, and (2) the subset of
patients that undergo macroscopically incomplete resection or no surgery.
Progress: This protocol received final approval on 9 January 2006; however, the ACOSOG
terminated the study due to lack of accrual in March 2006. No subjects enrolled at MAMC.
389
Detail Summary Sheet
Date: 30 Sep 06 Number: 205097 Status: Terminated
Title: Biological Relevance of Sentinel Lymph Node (SLN) Micrometastasis in Patients With
Colon Carcinoma
Principal Investigator: LTC Tommy A. Brown, MC
Department: Surgery/General Surgery Facility: MAMC
Associate Investigator(s): LTC Gregory P. Fitzharris, MC; MAJ James A. Sebesta, MC; MAJ
Alec C. Beekley, MC; LTC Robert M. Rush, MC
Start - Completion: Funding: Periodic Review:
Never approved DCI N/A
Study Objective: The objective of this study is to determine the prognostic significance of
molecular staging of colon carcinoma on the basis of sentinel lymph node mapping and analysis.
Technical Approach: Up to 200 male or female military health care beneficiaries over the age of
18 with a diagnosis of biopsy-proven, primary, non-metastatic (Clinical Stage I-III) colon
carcinoma will be enrolled in this study over a 3-4 year period. Subjects with colonic masses
clinically consistent with colon cancer will also be enrolled. Those subjects with masses clinically
consistent with cancer will be dropped if a diagnosis of colon cancer is not confirmed by pathology.
Specimen collection and pathologic processing will be conducted as described in the master
protocol. Patients will be followed for signs and symptoms of disease recurrence post-operatively
according to standard of care that consists of history and physical examination and serum CEA
every three months for 2 years, then every 6 months for two years then annually. A CXR will e
performed annually following primary colon resection. A colonoscopy will be performed on year
and three years post-operatively. If the 3 year post-op colonoscopy is normal, then follow-up will be
performed every 5 years thereafter.
Progress: This protocol received initial IRB approval with stipulations, 28 Jun 05; however, the
PI terminated the study prior to final approval in October 2006, as the Department of Pathology
could not support the study.
390
Detail Summary Sheet
Date: 30 Sep 06 Number: 203077 Status: Expired
Title: Comparative Medical/Surgical Research and Development (Limited)
Principal Investigator: LTC Tommy A. Brown, MC
Department: Surgery/General Surgery Facility: MAMC
Associate Investigator(s): None.
Start - Completion: Funding: Periodic Review:
4/16/2003 - Apr 2006 DCI 7/12/2006
Study Objective: 1) To facilitate preliminary investigations of proposed animal research models
and pilot studies, as well as the practice of newly described surgical procedures on animals prior to
use in human patients in an effort to refine and reduce the sacrifice of animals and enhance the
quality and effectiveness of medical/surgical patient services at MAMC. 2) To provide uniform
standards and assurances of proper animal care and use in the conduct of limited animal model
development, pilot studies and surgical advancement training proposed by MAMC -affiliated
medical staff.
This protocol is designed to facilitate preliminary investigative medical and surgical
research and development as described below: a) Development or refinement of animal models for
medical/surgical research or training, b) Limited pilot studies (animal) that are preliminary to
more extensive research proposals, c) Practice of newly described surgical procedures, animal
models prior to utilization in the MAMC human surgical patient population.
Technical Approach: The details of experimental design and general procedures will be provided
in each addendum to this protocol. The MAMC/DCI veterinarian (PI) will be consulted in the
development of all addenda to this protocol.
1. Proposed animal model development/refinement will be based on previously described animal
models that are considered to be flawed, recognized similarities in comparative
physicological/anatomical characteristics of particular animal species and humans or similarities
in disease processes. Pilot studies will likewise reference applicable similarities in comparative
physological/anantomical features between proposed animal models and humans as related to the
investigative question posed in the study. Practice of newly described surgical procedures will be
conducted on animal species possessing the most comparable organ systems of interest, then
compared to human anatomy and physiology.
2. Where applicable, animals will receive species-specific pre-anesthetic medication, anesthesia
and post surgical analgesia (as applicable ) as described in Section V.C.2.b., 3. a. and 7.b (1) of
Technical Methods. Requirements for pre, intra and/or post-operative biosample (e.g. blood, urine,
etc) collection or diagnostic imaging ( e.g. radiography ultrasonography, etc.) will be describved in
Section V.C.3.b, and e. of Technical Methods in each procedure-specific addendum.
3. Procedural descriptions and post-operative care instructions will be provided in Sections
V.C.2.a and b. of Technical Methods and V.D.l. and 2. of Veterinary Care in each addendum.
Methods of euthanasia and study endpoints will be described in Section V.C.3.5. and 6. of the
Technical Methods in each addendum.
Progress: One amendment was submitted to do a pilot study, using pigs, to develop a urinary
diversion technique to teach urology residents during laparoscopic training. Two pigs were used
successfully and this technique will be incorporated into future urology laparoscopic training labs.
391
Detail Summary Sheet
Date: 30 Sep 06 Number: 206110 Status: Ongoing
Title: Comparative Medical/Surgical Research and Development (Limited)
Principal Investigator: LTC Tommy A. Brown, MC
Department: Surgery/General Surgery Facility: MAMC
Associate Investigator(s): LTC Matthew J. Martin, MC; MAJ James A. Sebesta, MC; CPT
Matthew J. Eckert, MC; CPT Jason T. Perry, MC
Start - Completion: Funding: Periodic Review:
7/12/2006 - Jul 2009 DCI N/A
Study Objective: To facilitate preliminary investigations of proposed animal research models and
pilot studies, as well as the practice of newly described surgical procedures on animals prior to use
in human patients in an effort to refine and reduce the sacrifice of animals and enhance the
quality and effectiveness of medical/surgical patient services at MAMC.
To provide uniform standards and assurances of proper animal care and use in the conduct of
limited animal model development, pilot studies and surgical advancement training proposed by
MAMC-affiliated medical staff.
This protocol is designed to facilitate preliminary investigative medical and surgical research and
development as described below: a) Development or refinement of animal models for
medical/surgical research or training, b) Limited pilot studies (animal) that are preliminary to
more extensive research proposals, c) Practice of newly described surgical procedures, animal
models prior to utilization in the MAMC human surgical patient population.
Technical Approach: The details of experimental design and general procedures will be provided
in each addendum to this protocol. The MAMC/DCI veterinarian (PI) will be consulted in the
development of all addenda to this protocol.
1. Proposed animal model development/refinement will be based on previously described animal
models that are considered to be flawed, recognized similarities in comparative
physiological/anatomical characteristics of particular animal species and humans or similarities in
disease processes. Pilot studies will likewise reference applicable similarities in comparative
physiological/anatomical features between proposed animal models and humans as related to the
investigative question posed in the study. Practice of newly described surgical procedures will be
conducted on animal species possessing the most comparable organ systems of interest, then
compared to human anatomy and physiology.
2. Where applicable, animals will receive species-specific pre-anesthetic medication, anesthesia
and post surgical analgesia (as applicable) as described in Section V.C.2.b., 3. a. and 7.b (1) of
Technical Methods. Requirements for pre, intra and/or post-operative bio-sample (e.g. blood,
urine, etc) collection or diagnostic imaging (e.g. radiography ultrasonography, etc.) will be
described in Section V.C.3.b, and e. of Technical Methods in each procedure -specific addendum.
3. Procedural descriptions and post-operative care instructions will be provided in Sections
V.C.2.a and b. of Technical Methods and V.D.l. and 2. of Veterinary Care in each addendum.
Methods of euthanasia and study endpoints will be described in Section V.C.3.5. and 6. of the
Technical Methods in each addendum.
392
Progress: One amendment was approved for the prior protocol of the same title and carried into
this new protocol. The amendment, using four pigs for a pilot study to establish a hemorrage
model, it was unsuccesful. No further work will be done, this protocol will be terminated in Nov
2006.
393
Detail Summary Sheet
Date: 30 Sep 06 Number: 205112 Status: Ongoing
Title: RTOG 0412 / SWOG S0332, Phase III Randomized Trial of Preoperative Chemotherapy
Versus Preoperative Concurrent Chemotherapy and Thoracic Radiotherapy Followed By
Surgical Resection and Consolidation Chemotherapy in Favorable Prognosis Patients with Stage
IIIA (N2) Non-Small Cell Lung Cancer
Principal Investigator: LTC Tommy A. Brown, MC
Department: Surgery/General Surgery Facility: MAMC
Associate Investigator(s): MAJ James A. Sebesta, MC; MAJ Alec C. Beekley, MC; LTC John
B. Halligan, MC; LTC William B. Reece, MC; MAJ Angela G. Mysliwiec, MC; MAJ Jasmine T.
Daniels, MC; LTC David E. McCune, MC
Start - Completion: Funding: Periodic Review:
12/15/2005 - Aug 2010 SWOG via Henry M. Jackson Foundation 7/10/2006
Study Objective: (1) To prove that the preoperative regimen, consisting of thoracic radiation
therapy given concurrently with chemotherapy followed by surgical resection, results in a
significant improvement in overall survival compared to preoperative chemotherapy alone followed
by surgical resection, with both arms receiving postoperative consolidation therapy (2) comparison
of progression-free survival, median survival time, and toxicity and response rates (clinical and
pathologic) in both treatment arms (3) evaluate the correlation of the pCR with the disease-free
and overall survival (4) to investigate the association of DNA damage repair genes (ERCCl and
XRCCl), microtubule- related proteins (TUBB-III and MAP4), and shed tumor DNA with patient
responses and outcomes to the platinum/taxane/radiation therapy in this trial (5) to employ
MALDI-TOF proteomic analysis of tumor and serum to identify protein profiles associated with
response to therapy and prognosis (6) to evaluate the role of FDG-PET post-therapy in predicting
long-term outcome, as well as pathological response both in the tumor and in the mediastinal
lymph nodes (7) to assess patient-reported functional status as an endpoint with potentially
relevant differences between the two arms and (8) to determine the impact of co-morbid conditions
on survival.
Technical Approach: This study is a randomized trial of preoperative chemotherapy versus
concurrent chemoradiation followed by resection and consolidation in patients with Stage IIIA
NSCLC. Up to 547 subjects will be enrolled in this study over a period of approximately four years
with up to 6 subjects a year expected to enroll at MAMC. Patients in the chemotherapy arm will
receive induction therapy with CDDP at 75 mg/m2 on Days 1 and 22. Patients on the
chemoradiation arm will receive CDDP at 50 mg/m2 on days 1, 8, 22, and 29, with concurrent
radiation therapy delivered 5 days a week for a total of 50.4 Gy. Both groups will be reevaluated 3
to 5 weeks after induction, and then continue to resection if there is no progression of disease.
Patients in both arms will receive consolidation chemotherapy 4 to 6 weeks after surgery.
Consolidation will consist of Docetaxel, 75 mg/m2 on Days 1, 22 and 43, with growth factor support
24 hours after each chemo dose. Randomization to either arm will be stratified based on extent of
nodal involvement, nodal micro-metastases, and T stage. Follow-up visits will be done every 3
months for the first year, every 6 months for 2 years, then annually until death.
Included within this protocol are translational research, proteomics, FDG-PET and quality of life
studies. Blood and tissue samples will be submitted from biopsy and resection specimens. Copies of
pre- and post-induction scans will be submitted. Some of these studies are optional, and are
specifically addressed in the consent form. ERCCl, XRCCl, TUBB-III and MAP4 are all genetic
markers that have been associated with susceptibility or resistance to various chemotherapy
agents. Levels of these markers will be correlated with patient outcomes. Shed Tumor DNA can be
detected in patient plasma, and will be examined for a response to presence or lack of tumor.
394
Proteomic analysis by MALDI-TOF will be done to attempt to correlate several known proteomic
patterns with patient outcome. FDG-PET data will be examined to define its usefulness in imaging
the status of nodal disease in these patients.
Progress: This protocol remains open to enrollment with no patients enrolled.
395
Detail Summary Sheet
Date: 30 Sep 06 Number: 205113 Status: Completed
Title: SWOG 9430, A Phase II Trial of Complete Surgical Resection for Stage IV Melanoma -
Surgical Resection With Biological Evaluation And Clinical Follow-Up
Principal Investigator: ETC Tommy A. Brown, MC
Department: Surgery/General Surgery Facility: MAMC
Associate Investigator(s): MAJ James A. Sebesta, MC; MAJ Alec C. Beekley, MC
Start - Completion: Funding: Periodic Review:
11/30/2005 - Aug 2010 SWOG via Henry M. Jackson Foundation N/A
Study Objective: (1) To assess the overall survival and progression-free survival of patients with
metastatic melanoma (beyond the draining lymph nodes) following complete surgical resection of
all known disease. (2) To determine the ability of the Southwest Oncology Group Melanoma
Committee to enroll patients with metastatic melanoma who can be resected to a 'disease-free'
state. This will assess the feasibility of future trials of specific interventions in this patient
population.
Technical Approach: This study will enroll patients who have completely respectable metastatic
melanoma who are appropriate for surgery alone. Clinical data will be collected to determine what
clinical factors are associated with improved survival. Biologic samples for correlative studies on
melanoma will be collected in the companion protocol SWOG 9431. A total of 100 eligible patients
will enrolled on this study with up to two patients a year enrolled at MAMC. Patients will be
consented and registered prior to surgery. Baseline evaluations include history and physical,
laboratory tests, and disease assessment by CT, MRI or X-ray as appropriate. Follow-up after
surgery will include physical exam, laboratory tests and disease assessment every 3 months for 1
year. The primary endpoint is survival. With 100 eligible patients, the one year survival rate can
be estimated to within +/- 10%.
Progress: SWOG reported permanent closure of this protocol in December 2005, due to limited
accrual over the past year. No subjects enrolled at MAMC.
396
Detail Summary Sheet
Date: 30 Sep 06 Number: 205114
Status: Completed
Title: SWOG 9431, Cytogenetic Molecular and Cellular Biology Studies
Patients, Ancillary
in Metastatic Melanoma
Principal Investigator: ETC Tommy A. Brown, MC
Department: Surgery/General Surgery
Facility: MAMC
Associate Investigator(s): MAJ James A. Sebesta, MC; MAJ Alec C. Beekley, MC
Start - Completion: Funding:
11/8/2005 - Aug 2010 SWOG via Henry M. Jackson Foundation
Periodic Review:
N/A
Study Objective: (1) To characterize the frequency of non-random cytogenetic abnormalities in
regional and distant melanoma metastases and explore their association with clinical outcome of
melanoma patients enrolled onto SWOG trials. (2) To characterize the frequency of specific genetic
alterations at the DNA, mRNA, or protein level and explore the association of these abnormalities
with clinical outcome in patients with regional and distant metastases who are enrolled on SWOG
melanoma trials. The specific genes to be studied in this protocol include pl6 and nm23. (3) To
characterize the host immunologic response to metastatic melanoma by determining the whether
the in vivo pattern of cytokine expression is consistent with specific subsets of T helper cells within
melanoma deposits. To explore whether host immunologic response varies based on the site of
metastatic disease and/or correlates with clinical outcomes in patients enrolled on SWOG trials.
(4) To obtain peripheral blood, sera and paraffin embedded tumor blocks from patients with
metastatic melanoma to create a tissue, cell and sera bank for future studies. (5) To attempt to
correlate the most prevalent gene copy alterations observed in metastatic disease with the risk of
progression in paraffin-embedded tissue samples collected in SWOG-9035 in patients with primary
melanoma.
Technical Approach: This study plans to collect samples from patients enrolled in SWOG
melanoma trials. Blood, serum, paraffin-embedded tissue and flash frozen tissue will be collected
and stored to support future studies on the relationship of cytogenetics, immunological response,
and genetic alterations in melanoma to patient outcomes. Enrollment in this study is a
requirement for enrollment in the SWOG 9430 study of complete surgical resection in metastatic
melanoma.
Progress: SWOG reported permanent closure of this protocol in December 2005, due to the
closure of associated treatment protocols. No subjects enrolled at MAMC.
397
Detail Summary Sheet
Date: 30 Sep 06 Number: 202013 Status: Ongoing
Title: Bariatric Surgery Effects on the Comorbidities of Obesity
Principal Investigator: COL (Ret) Preston L. Carter, MD
Department: Surgery/General Surgery Facility: MAMC
Associate Investigator(s): CPT Craig S. See, MC; MAJ James A. Sebesta, MC; COL David M.
Watts, MC; ETC Robert M. Rush, MC; Margaret I. Voelker, RN, CRC; MAJ Philip S. Mullenix,
MC; COL Kenneth S. Azarow, MC; COL (Ret) William E. Eggebroten, MD; MAJ Alec C. Beekley,
MC; CPT Zachary M. Arthurs, MC; CPT Daniel G. Cuadrado, MC; CPT Katharine E. Wolcott,
MC
Start - Completion: Funding: Periodic Review:
10/24/2001 - Mar 2006 DCI 9/26/2006
Study Objective: To determine and compare the effectiveness of resectional and laparoscopic
gastric bypass in regards to reducing the comorbidities and mortality associated with morbid
obesity.
Technical Approach: This study is a prospective observational study to analyze the effects of
resectional and laparoscopic bypass on the morbidity and mortality of morbid obesity. All patients
undergoing bariatric surgery at MAMC will be included in the study. A history, examination, and
labs will be done preop, 3-6-and 12 months post-op. The variables and outcomes measured will
include: weight, insulin/oral hyperglycemic requirement, fasting glucose, Hbalc, anti-lipid
requirement, total cholesterol, LDL, HDL, triglycerides, antihypertensive requirement, blood
pressure, sleep apnea screening questions, joint pain, panniculitis, hemoglobin, hematocrit, MCV,
FE+, Ca+, vitamin B12, folate, prealbumin, and complications. Analysis of these outcomes of
surgery will add significantly to the rationale behind bariatric surgery.
Progress: This prospective observational protocol remains open to patient entry, with 339
bariatric surgery patients enrolled, 127 during FY06. Ten patients withdrew prior to screening or
having their surgical procedure. Data collection on enrolled patients continued at MAMC during
FY06.
398
Detail Summary Sheet
Date: 30 Sep 06 Number: 204001 Status: Ongoing
Title: Does Intestinal Fatty Acid Binding Protein Predict Strangulation in Mechanical Small
Bowel Obstruction?
Principal Investigator: CPT Daniel R. Cronk, MC
Department: Surgery/General Surgery Facility: MAMC
Associate Investigator(s): CPT Daniel G. Cuadrado, MC; CPT Troy P. Houseworth, MC; CPT
Patrick M. McNutt, MS; COL Kenneth S. Azarow, MC; CPT Randy J. Kjorstad, MC
Start - Completion: Funding: Periodic Review:
10/24/2003 - Dec 2003 DCI 10/10/2006
Study Objective: To determine if intestinal fatty acid binding protein (I-FABP) levels are
elevated in patients with strangulated mechanical small bowel obstruction.
Technical Approach: This is a prospective, observational, pilot study investigating the utility of
intestinal fatty acid binding protein (I-FABP) for detecting strangulated mechanical small bowel
obstruction. Thirty consecutive patients presenting to the general surgery service with mechanical
bowel obstructions will be enrolled and have plasma and urine I-FABP levels analyzed at the time
of admission, time of operation, and 24 hours after operation (should they require operative
intervention). Using multivariate analysis, levels of plasma and urine I-FABP will be compared
between those patients without ischemia and those with ischemia upon operative exploration to
determine if I-FABP is a potentially useful marker for the prospective identification of
strangulated small bowel obstruction.
Progress: This protocol is open to patient entry, with no additional patients enrolled during FY06.
Investigators plan to re-initiate enrollment within the next several weeks as more research
personnel become available. To date, 45 subjects have been enrolled; 30 hospital patients with
bowel obstructions (among these 3 "positives" that had ischemic bowel), ten normal controls and
five dialysis patients.
399
Detail Summary Sheet
Date: 30 Sep 06 Number: 206040 Status: Ongoing
Title: Does SDF-1 Production by Atherosclerotic Plaques Correlate with Severity of Carotid
Artery Stenosis?
Principal Investigator: CPT Daniel R. Cronk, MC
Department: Surgery/General Surgery Facility: MAMC
Associate Investigator(s): CPT Garth S. Herbert, MC; COL (Ret) Charles A. Andersen, MD;
LTC Benjamin W. Starnes, MC; MAJ Kelly S. Blair, MC; CPT Jason T. Perry, MC
Start - Completion: Funding: Periodic Review:
1/5/2006 - Dec 2006 DCI 12/8/2006
Study Objective: To determine whether levels of SDF-1 as measured in atherosclerotic plaques
correlates with the severity of disease.
Technical Approach: Blood will be drawn from patients scheduled to undergo carotid
endarterectomy at the time of surgery or pre-operative evaluation to determine serum SDF-1
levels. In addition, a small section of plaque will be removed from the atherosclerotic plaque
excised from twenty patients undergoing carotid endarterectomy at MAMC. The remainder of the
plaque will be sent for routine pathological analysis (as is the standard at MAMC). The portion of
the specimen used for study purposes will be brought to the Department of Clinical Investigation,
where the presence of SDF-1 and possibly other inflammatory mediators will be established using
immunohistochemical methods. Segments of radial artery harvested at the time of coronary artery
bypass graft will be used as negative controls for immunohistochemical staining. Blood from
healthy volunteers will be drawn for control values of serum SDF-1 levels. Regression analysis will
be performed to attempt to determine a relationship between the level of SDF-1 in serum/plaques
to the degree of carotid artery stenosis.
Progress: No patients have been enrolled to date. Responsibility for the bench portion of the study
(immunohistochemistry and performance of ELISA) will likely be passed to a new research
resident after submission of appropriate amendments. Clinical responsibilities have prevented the
current investigators from initiating this study.
400
Detail Summary Sheet
Date: 30 Sep 06 Number: 206041
Status: Ongoing
Title: Breast Abscesses Following Nipple Piercing: A Case Series and Review of the Literature
Principal Investigator: CPT Daniel G. Cuadrado, MC
Department: Surgery/General Surgery
Facility: MAMC
Associate Investigator(s): MAJ Alec C. Beekley, MC; COL (Ret) Preston L. Carter, MD
Start - Completion: Funding:
1/5/2006 - Feb 2006 DCI
Periodic Review:
12/8/2006
Study Objective: To review out institutional experience with the treatment of breast abscesses
following nipple piercing.
Technical Approach: A chart review will be performed and patients separated into 2 groups
based upon whether or not they have a pierced nipple on the infected side. Demographic data will
be collected and analyzed between the two groups such as age, sex, date of piercing, date of
surgery, number of surgical procedures and organism found in the abscess cavity. Data will be
analyzed using a t-test for continuous and Chi square for categorical data.
Progress: Eight patients over the five year time period were identified who had abscesses due to
nipple piercing. When compared to all breast abscesses treated operatively over that time, these
patients had a significantly higher rate of requiring a second operation. An abstract was submitted
to the Southwest Surgical Society for possible presentation and the work will be submitted for
publication to the American Journal of Surgery during FY07.
401
Detail Summary Sheet
Date: 30 Sep 06 Number: 203114 Status: Completed
Title: Chewing Gum for the Reduction of Postoperative Ileus After Elective Open Colectomy
Principal Investigator: CPT Daniel G. Cuadrado, MC
Department: Surgery/General Surgery Facility: MAMC
Associate Investigator(s): CPT Daniel R. Cronk, MC; LTC Gregory P. Fitzharris, MC
Start - Completion: Funding: Periodic Review:
9/29/2003 - Nov 2006 DCI 8/23/2005
Study Objective: To determine the efficacy of chewing gum at hastening the return of bowel
function after major open abdominal surgery.
Technical Approach: This is a prospective, randomized, open-label trial evaluating chewing gum
versus standard early resumption of oral intake for the reduction of postoperative ileus after open
colon resection. A total of 36 consecutive patients ages 18-85 will be preoperatively randomized to
receive either chewing gum or early oral intake starting on postoperative day number one.
Patients will record precisely the time of their first postoperative flatus and tolerance of solid food.
Time to hospital discharge will also be evaluated. Time to first flatus, time to tolerance of solid
food, and length of hospital stay will be compared between the two groups using student's t-test.
Progress: This protocol was reported completed with 29 of 38 subjects enrolled. Accrual was
halted early because the Department of Surgery has made a move to primarily laparoscopic colon
surgery and further enrollment would likely be limited at best. Data so far goes along with several
recently published studies on the effects of gum; this small experience should add to the literature.
402
Detail Summary Sheet
Date: 30 Sep 06 Number: 206016 Status: Terminated
Title: Determining the Incidence of Sonographically Detectable Wound Seromas in the Morbidly
Obese: A Pilot Study
Principal Investigator: CPT Daniel G. Cuadrado, MC
Department: Surgery/General Surgery Facility: MAMC
Associate Investigator(s): CPT Katharine E. Wolcott, MC; CPT Matthew J. Eckert, MC; MAJ
Joseph A. Ronsivalle, MC; MAJ James A. Sebesta, MC; COL (Ret) Preston L. Carter, MD
Start - Completion: Funding: Periodic Review:
10/28/2005 - May 2005 DCI N/A
Study Objective: To determine the rate of clinically significant and sub -clinically detectable
wound seromas following open surgery in the morbidly obese.
Technical Approach: This descriptive study will examine the morbidly and super obese
population (BMI 40-60) to determine the sonographic incidence of wound seromas following open
bariatric surgery. Thirty consecutive obese patients undergoing bariatric surgery will be enrolled
and undergo a pre-operative ultrasound of the planned surgical site by General Surgery Residents,
in the pre-operative holding area, with the Sonosite® portable ultrasound to ensure that no pre¬
operative fluid collections are present. At the two week and one month post-operative visits, they
will undergo repeat sonographic evaluation by a member of the research team. During the two and
four week evaluation, the patients will have the length of their incision measured. At 2 cm
intervals along the length of the incision (starting 4cm above and 4cm below the incision),
consecutive measurements will be made to determine the width and depth of the fluid collection.
The dimensions of the fluid collection will be tabulated and used to determine the area and volume
of the seroma (VEllipse = length x width x depth x 0.5233). The presence or absence of wound
infection or drainage from the wound will likewise be recorded. Any fluid collections identified will
be brought to the attention of the attending surgeon. Standard treatment for symptomatic or
infected seromas is drainage. Asymptomatic and subclinical seromas are normally followed, but
this decision will be left to the attending surgeon.
All General Surgery residents obtain annual ultrasound training as part of the core curriculum.
The sonographic examinations for this study will be performed only by the PI and AIs who will
receive additional training from the Department of Radiology for the purposes of this study.
Likewise, the images will be stored (labeled only with the code list identifier) so that the recorded
measurements can be independently verified. The ultrasound device to be used will be the Sonosite
from the General Surgery Clinic that residents are trained on.
Progress: The ultrasound device used could not get accurate reproducible pictures and more
laparoscopic gastric bypass procedures are being performed compared to RGBs. This protocol was
terminated during FY06, due to low accrual and it was no longer feasible to continue the study.
403
Detail Summary Sheet
Date: 30 Sep 06 Number: 203034 Status: Ongoing
Title: Impact of Gastric Bypass with Subtotal Gastrectomy on Plasma Ghrelin Profile
Principal Investigator: CPT Daniel G. Cuadrado, MC
Department: Surgery/General Surgery Facility: MAMC
Associate Investigator(s): MAJ Philip S. Mullenix, MC; COL Kenneth S. Azarow, MC; CPT
Daniel R. Cronk, MC; CPT Craig S. See, MC; CPT Patrick M. McNutt, MS; COL (Ret) Preston L.
Carter, MD; MAJ Alec C. Beekley, MC; CPT Zachary M. Arthurs, MC; CPT Garth S. Herbert,
MC; CPT Katharine E. Wolcott, MC; LTC Matthew J. Martin, MC
Start - Completion: Funding: Periodic Review:
5/8/2003 - Dec 2003 DCI 3/22/2005
Study Objective: To compare the preoperative, immediate postoperative, and 3 month
postoperative plasma ghrelin profiles among a cohort of patients undergoing resectional gastric
bypass (subtotal gastrectomy combined with roux-en-y bypass). To compare the pre and
postoperative plasma leptin and insulin profiles among this patient cohort. To document the
change in gross weight, body mass index, and blood pressure among this cohort.
Technical Approach: This study will prospectively compare the preoperative and postoperative
levels of ghrelin, leptin and insulin in a cohort of patients undergoing resectional gastric bypass.
Hormone levels will be obtained one day prior to surgery, two days after surgery, and at three to
four months after surgery. Eighteen-hour profiles for each hormone will be generated and area
under the curve calculated for comparison. Postoperative complications, amount of weight change,
change in body mass index, and change in blood pressure will be recorded and analyzed.
Statistical analysis will be done using two-tailed paired Student's t-test where appropriate.
Progress: This protocol remains ongoing, with 2 subjects enrolled. Based on recent published data
with Ghrelin, investigators plan to revise the original protocol and change the total number of
blood draws to four. This would be a major reduction in the amount of blood draws and reduction
in the risk of the procedure.
404
Detail Summary Sheet
Date: 30 Sep 06 Number: 206047 Status: Completed
Title: Bronchoscopy in the Blast Injury Patient
Principal Investigator: CPT Matthew J. Eckert, MC
Department: Surgery/General Surgery Facility: MAMC
Associate Investigator(s): COL Kenneth S. Azarow, MC
Start - Completion: Funding: Periodic Review:
1/24/2006 - Dec 2007 DCI N/A
Study Objective: The purpose of this study is to evaluate respiratory symptom development and
fiberoptic bronchoscopy findings in a series of blast injured patients in Operation Iraqi Freedom
(OIF).
Technical Approach: This study is a retrospective review of tourniquet use among all patients
with major extremity injuries who presented to the 31st Combat Support Hospital in Iraq, in
support of Operation Iraqi Freedom. An existing database of approximately 30 subjects will be
reviewed. Collected data includes mechanism of injury, type of blast, associated burns, and
requirement for endotracheal intubation, vital signs, time sequence between point of injury and
presentation of pulmonary injury symptoms, therapeutic interventions performed, and
bronchoscopic findings. Statistical analysis will be performed to examine whether therapeutic
intervention prevented the need for endotracheal intubation and to identify variables associated
with requirement for intubation. Conclusions will help to better inform medical personnel treating
blast injury patients of the incidence and associated injury pattern in those patients with delayed
airway injury manifestation, and the time interval between injury and delayed symptom
development.
Progress: This review of 23 blast injured Soldiers demonstrated that delayed manifestation of
secondary airway injury may require up to 18 hours of observation in an acute care setting due to
the significant incidence of delayed airway edema symptoms in this population. The results of this
study were presented at the annual meeting of the Pacific Coast Surgical Association, 19 Feb 2006,
and were awarded "Best Resident Paper Competition" winner. The manuscript was published in
Aug 2006 Archives of Surgery.
405
Detail Summary Sheet
Date: 30 Sep 06 Number: 206115
Status: Ongoing
Title: Hypoxemic Reperfusion Following Lower Torso Ischemia in sp. Sus scrofa
Principal Investigator: OPT Matthew J. Eckert, MC
Department: Surgery/General Surgery
Facility: MAMC
Associate Investigator(s): ETC Matthew J. Martin, MC;
T. Perry, MC
CPT Vance Y. Sohn, MC; CPT Jason
Start - Completion: Funding:
8/9/2006 - Aug 2009 DCI
Periodic Review:
N/A
Study Objective: Hypothesis is that hypoxemic reperfusion (Pa02 30-35mmHg) compared with
normoxemic reperfusion (Pa02 lOOmmHg) following lower torso ischemia induced by supra-celiac
aortic cross-clamping results in improved hemodynamic stability and pulmonary gas-exchange,
decreased vasoactive medication requirements, decreased reperfusion injury induced
histopathologic changes in multiple organ systems, and less evidence of reactive oxygen species
activity. Additionally, hypothesize that the hypoxemic reperfusion strategy will limit the hind-leg
compartment pressure compared to normoxemic reperfusion.
Technical Approach: V.l. Experimental Design and General Procedures: This experiment will
be conducted in a multi-phase format, beginning with a pilot study to determine the feasibility of
our model. This general protocol will cover the basics of the overall experimental goal, but
subsequent amendments will detail successive phases as dictated by success of the pilot study and
refinement of various techniques.
Phase I (Pilot Study): The pilot study will utilize a total of four pigs. After establishment of general
anesthesia, arterial vascular access will be obtained for continuous pressure monitoring at the
common carotid or femoral artery using a cut- down approach and Seldinger cannulation
technique. Hind leg compartment pressure will be monitored continuously using an arterial
catheter placed percutaneously into a hind-leg musculo-fascial compartment. Venous access via
the jugular vein will be obtained for intra-venous fluid and medication administration. An
additional lower extremity vein (likely femoral vein) will be accessed for sampling of the ischemic
region of the body. Ventilatory parameters will be adjusted to maintain baseline blood gas
parameters during the access and ischemia portions of the experiment (Pa02 70-90mmHg, PC02
40-50, pH 7.4-7.55 and saturations of 92-98%) After baseline stabilization and laboratory analysis
(blood gas, lactate, chem.-7 panel), a midline laparotomy will be performed with cross-clamping of
the supra-celiac aorta for 60 minutes. A supra-pubic bladder catheter will be placed to allow for
measurement of urine production during the ischemic and reperfusion phases. Prior to the end of
60 minutes of ischemia repeat lab samples will be performed. During the last 10 minutes of
ischemia ventilatory management will alter the Pa02 to a goal of 30-35mmHg by decreasing the
fraction of inspired 02 (Fi02), for the hypoxemic reperfusion group (HR). The normoxemic
reperfusion group (NR) will enter the reperfusion phase with a goal Pa02 of 95-105mmHg. Once
these ventilatory parameters are met, the cross-clamp will be released, with serial hemodynamic
measurements every 15 minutes during the 120 minute reperfusion phase with repeat lab
sampling every 30 minutes and continuous compartment pressure monitoring. During the
ischemic and reperfusion phase lactated ringer's fluids and epinephrine will be used as needed to
maintain the baseline MAP (Douzinas et al. Crit Care Med 2003;31:2183 found that 50ug/min i.v.
epinephrine just prior to cross-clamp release and as need thereafter prevented immediate cardiac
arrest). The total intra-venous fluid and pressor medication requirements will be recorded for
comparison. The protocol of ventilatory management for the HR group during the reperfusion
phase is as follows: 10 minutes of a goal Pa02 of 30-35mmHg, followed by gradual increase of the
Fi02 to achieve a goal Pa02 of 50mmHg at 60 minutes reperfusion and finally lOOmmHg at 120
406
minutes of reperfusion. Following reperfusion completion and final lab/hemodynamic value
recording, the animals will be euthanized.
V.1.2. Phase II: Following confirmation of our experimental model from Phase I, we plan to
conduct a full trial of hypoxemic vs. normoxemic reperfusion with additional biochemical and
pathologic analysis evaluating the activity and effects of reactive oxygen species. The ischemia-
reperfusion model will be identical unless found to require modification during the pilot and
appropriately addressed in an addendum. Phase II will include post-mortem tissue sampling of
lung, liver, kidney and brain for histopathologic evidence of ischemia/inflammatory changes. This
will be conducted by two pathologists unaware of the animal's reperfusion strategy, with organ
injury graded by a predetermined scale. Inter-observer variability will be calculated. Additional
biochemical analysis during Phase II will include measurement of free radical activity and effects.
This will be conducted using venous whole blood samples with commercially available kits for
oxygen free radical activity and superoxide dismutase (Trevigen, Gaithersburg, MD) assays, along
with determination of xanthine oxidase activity (Invitrogen, USA). The detrimental effects of lipid
peroxidation by free radicals will be determined with malonaldehyde (MDA) and hydroxyalkenal
assays of whole blood samples (Calbiochem, San Diego, CA). We tentatively plan to use a total of
20 pigs during Phase II, ten in each group. We reserve the right to change the commercial assay
kits if a cheaper, equivalent product is found in order to reduce the cost of this experiment. Such
changes would be detailed in subsequent amendments as needed.
V.1.3. Phase III: Phase III is a potential further experimental trial evaluating the beneficial effects
of known free radical scavengers (mannitol, allopurinol, superoxide dismutase) in concert with a
hypoxemic reperfusion strategy for improved control/modulation of the reactive oxygen species
contribution to reperfusion injury. This Phase will be addressed in a future amendment pending
successful completion of Phase I/II and statistical analysis to determine the number of animals
required to show a significant difference between treatment groups.
Progress: Protocol was recently approved, will begin in FY 2007.
407
Detail Summary Sheet
Date: 30 Sep 06 Number: 205080
Status: Ongoing
Title: Stem cell engraftment in the lipopolysaccharide mouse
inflammatory injury
(Mus musculus) model of acute
Principal Investigator: CPT Matthew J. Eckert, MC
Department: Surgery/General Surgery
Facility: MAMC
Associate Investigator(s): CPT Daniel R. Cronk, MC; CPT Daniel G. Cuadrado, MC; CPT
Kerry L. O’Brien, MC; COL Kenneth S. Azarow, MC; CPT Garth S. Herbert, MC
Start - Completion: Funding:
5/11/2005 - May 2008 DCI
Periodic Review:
5/10/2006
Study Objective: To investigate the most efficient conditions under which to administer stem
cells to mice following experimentally induced inflammatory injuries.
Technical Approach: This study will be carried out in four phases. The first phase will be a pilot
study to develop the LPS injury model in this laboratory, to further characterize a number of
molecules that play a role in stem cell movement but have not been studied in LPS injury, and to
accurately define the optimal timing for administration of cellular therapies to enhance their
eventual engraftment in the target tissue. LPS injuries in the lung and skeletal muscle will be
utilized. The first phase will also involve in vitro studies of the cultured bone marrow from mice
euthanized during this first phase. The in vitro studies will allow us to evaluate cell culture
treatments that may enhance the administered stem cells. To date, the pulmonary LPS injury has
been demonstrated reproducibly in our lab from our previous studies. To complete phase 1 similar
LPS challenges in skeletal muscle will be performed. This will be accomplished by intramuscular
injection of LPS with animal sacrifice at 0, 6, 12, 24, 48 and 72 hours. The muscle samples will be
analyzed by histology, immunohistochemistry and ELISA. The second phase of this study will
involve using various pro and anti-inflammatory cytokines to modulate the local immune response
following LPS induced injury. To date in our lab we have demonstrated that stromal derived
growth factor 1 (SDF-1) is modulated following LPS induced lung injury. This cytokine has been
previously demonstrated to be essential for stem cell engraftment following bone marrow
transplant. In order to further characterize the role of SDF-1 in inflammatory injury, we will
measure tissue levels following LPS challenge. Furthermore, through the use of cytokine delivery
systems we will characterize the effect of dyschronic administration of SDF-1 on the inflammatory
cascade. Using 100 micron heparin sulfate bonded acrylic beads injected into the subcutaneous
tissue (along with bupivicaine to reduce pain) we will examine the cellular response both in the
presence as well as in the absence of LPS. The third phase of this study will involve
transplantation of bone marrow into LPS injured mice and evaluation of engraftment into target
tissues at various time points. For this phase of the protocol, LPS will be administered through
either direct injection (i.e. intratracheally, intraperitoneally) or through a subcutaneous delivery
system in the thigh (heparin sulfate impregnated beads). The fourth phase of this study will
combine information from the first three phases and determine if the putatively successful
maneuvers evaluated in phase one actually enhance engraftment of transplanted bone marrow
cells.
Progress: This multi-phase project evaluating the effects of intra-peritoneal and intra-tracheal
LPS inoculation with regard to SDF-1 modulation continues, with good confirmatory results from a
second trial of IP inoculation. The results of the IT-LPS study were submitted to a major journal
for publication and we are currently preparing the IP-LPS results for submission as well. The next
phase of the project will utilize proteomic micro-array techniques to identify any associated
molecules related to SDF modulation. A separate amendment will be submitted next with details
of the upcoming steps in this project.
408
Detail Summary Sheet
Date: 30 Sep 06 Number: 204101
Status: Terminated
Title: Advanced Trauma Life Support (ATLS) Training Utilizing the Goat (Capra hircus)
Principal Investigator: COL (Ret) William E. Eggebroten, MD
Department: Surgery/General Surgery
Facility: MAMC
Associate Investigator(s): COL Kenneth S. Azarow, MC
Start - Completion: Funding:
7/14/2004 - Jul 2007 DCI
Periodic Review:
9/12/2005
Study Objective: To administer life saving care to trauma patients e.g. insertion of chest tube,
cricothyroidotomy, pericordiocentesis or diagnostic peritoneal lavage. This training will teach
physicians one safe method of perfoming these life saving procedures for trauma patients, as well
as optional venus cut-down. The use of animals will enhance the clinical skills and confidence of
the trainees during the training session. This will result in improved patient care during a
critical, emergency situation. Live animals are preferred in order to provide the closest simulation
to the real life-saving situation possible. Human cadavers and simulators have been used in the
past and have been judged to be less realiatic. The new Sim-Man (registered trademark)
simulator promises to more closely resemble simulation of the life-saving procedures and the ACS
is transitioning to this simulated model for its ATLS student courses. Cost considerations of
approximately an additional $2500 per course for use of this product must be recognized and for
this reason the faculty judge the Sim-Man an acceptable alternative to the live animal model when
additonal funding has been secured in the future.
Technical Approach: The ACS has developed a copyrighted course designed to educate
physicians in the basics of trauma care. As part of a 2-day course, an animal training module will
be incorporated. After the animals are adequately anesthetized, each procedure will be performed
as described below. A suitable vein is selected on the leg and an incision is made over it. The
vessel is isolated and a plastic catheter is placed inside of it. This allows fluid to be given rapidly.
Next, a diagnostic peritoneal lavage is performed. A small incision is made on the lower abdomen
and a long catheter is inserted into the abdominal cavity. Fluid is infused into the abdomen and
then removed for laboratory analysis. This allows the identification of intra-abdomen injury.
Following this, chest tube insertion is performed. This is accomplished by making a 1-2 inch
incision on the lower chest. A clamp is then bluntly placed through the space between the ribs into
the chest cavity. A large tube is placed through this hole, allowing drainage of fluid/blood and re¬
expansion of a collapsed lung. Pericardiocentisis is performed by placing a long needle through the
chest wall into the sac surrounding the heart. This allows removal of any blood that may be
compressing the heart. Prior to pericardiocentesis, the pericardium is filled with fluid by placing a
catheter within the pericardium. An anterolateral, left sided thoracotomy is performed by making
an incision in the left, fifth intercostal space extending from the sternum to the posterior axillary
line. All subcutaneous tissue, muscles and pleura are dissected with scissors or a scapel. Rib
retractors are placed to gain exposure. The pericardium is identified and incised. The catheter is
sutured into place and the pericardium is filled with fluid. Next a critcothyroidotomy is performed
by making an incision over the windpipe into the neck. Next, a cricothyroidotomy is performed by
making an incision over the windpipe into the neck. An incision is then made into the windpipe.
A tube is placed through the incision into the wind pipe in order to breathe for the patient. The
animal is euthanized prior to performing the cricothyroidotomy.
Progress: No labs run in FY 2005 or FY 2006, ATLS is using TraumaMan (non-animal alternate)
instead of live animal models. Protocol is terminated.
409
Detail Summary Sheet
Date: 30 Sep 06 Number: 204100
Status: Ongoing
Title: Human Blood Collection for Bench Research Initiatives
Principal Investigator: CPT Michael J. Hartenstine, MS
Department: Surgery/General Surgery
Facility: MAMC
Associate Investigator(s): CPT Daniel G. Cuadrado, MC; CPT Daniel R. Cronk, MC; CPT
Patrick M. McNutt, MS; CPT Garth S. Herbert, MC
Start - Completion: Funding:
7/16/2004 - Jul 2008 DCI
Periodic Review:
6/27/2006
Study Objective: To obtain blood samples from normal, healthy subjects for use in bench
experiments involving the behavior of blood cells in culture. To obtain blood samples from normal,
healthy subjects for use as controls in bench experiments (e.g., ELISA analyses).
Technical Approach: Prospective collection of tissue samples with subjects selected by
announcements asking for volunteers at meetings within DCI and DOS. Blood will be aseptically
obtained in an amount not to exceed 550ml from any one subject in any 8-week period. Not more
than two blood draws will be performed on any one subject in any one week period. Blood will
either be used immediately for bench experiments, or frozen and stored for use at a later date.
Samples will be de-linked from subjects at the time of blood draw. No additional information will
be obtained from subjects. Samples will not be transported out of the DCI. Samples will be
destroyed within one year of collection.
Progress: This protocol remains available to collect blood samples to be used as a source of cells
and other substances e.g. proteins from healthy subjects. One subject has enrolled.
410
Detail Summary Sheet
Date: 30 Sep 06 Number: 206026 Status: Ongoing
Title: Determination of Telomerase Activity in Atypical Ductal Hyperplasia of the Breast
Principal Investigator: CPT Garth S. Herbert, MC
Department: Surgery/General Surgery Facility: MAMC
Associate Investigator(s): LTC Tommy A. Brown, MC; COL Kenneth S. Azarow, MC; MAJ
Anne L. Champeaux, MC; CPT Matthew J. Eckert, MC; CPT Michael J. Mulcahy, MC
Start - Completion: Funding: Periodic Review:
12/14/2005 - Mar 2006 DCI N/A
Study Objective: Objective is to determine the presence and prognostic significance of telomerase
activity in breast atypical ductal hyperplasia.
Technical Approach: A review of Breast pathway charts will be completed to identify 20 patients
with a diagnosis of atypical ductal hyperplasia on core biopsy who went on to open surgical biopsy.
Ten of these patients will have ductal carcinoma in situ (DCIS) identified at open surgical biopsy
and ten will have benign pathology. Data will be coded and immunohistochemistry performed on
the paraffin slides of these tissues. The pathologic diagnosis on open surgical biopsy will be
compared and correlations made (if any) between intensity of staining and the presence/absence of
cancer on open surgical biopsy.
Progress: This bench protocol identified seventeen patients who underwent open surgical biopsy
following core biopsy that showed ADH. Testing was performed on old surgical specimens.
Telomerase staining was not predictive of which patients with ADH on core biopsy would go on to
have cancer on open surgical biopsy. A manuscript has been prepared for presentation at the
North Pacific Surgical Association meeting, and is being forwarded to DCI for review.
411
Detail Summary Sheet
Date: 30 Sep 06 Number: 206010 Status: Ongoing
Title: Does Control of Inflammation Prior to Intervention for Carotid Artery Disease or Lower
Extremity Peripheral Arterial Disease Affect Outcome?
Principal Investigator: CPT Garth S. Herbert, MC
Department: Surgery/General Surgery Facility: MAMC
Associate Investigator(s): COL (Ret) Charles A. Andersen, MD; LTC Benjamin W. Starnes,
MC
Start - Completion: Funding: Periodic Review:
2/6/2006 - Jul 2008 DCI 10/19/2006
Study Objective: This study will determine the effect that a 30-day course of aspirin and statins
have on inflammation, as measured by CRP levels and determine whether peri-operative
management of inflammation affects outcome (specifically re- stenosis / myointimal hyperplasia)
following intervention for Carotid Artery Stenosis or Peripheral Arterial Disease.
Technical Approach: Participants in this study will include up to 200 volunteers who require
intervention for CAS, in addition to 120 who require intervention for lower extremity PAD.
Patients will be randomized to either intervention alone (surgery or angioplasty/stenting)
accompanied by moderate statin therapy (standard of care for patients with atherosclerotic
disease), or a 90-day peri-operative course of atorvastatin and aspirin directed at reducing the
degree of systemic inflammation (to include 30 days pre-operatively and 60 days post-operatively).
CRP levels will be measured in each group at baseline, pre-operatively, and during follow up visits.
Subjects will undergo surgery for carotid artery stenosis, or intervention for lower extremity PAD.
Complications, to include myocardial infarction, stroke, death, and in particular, re-stenosis will
be measured in each group. The number of complications in each group (those simply undergoing
surgery, and those who have surgery accompanied by a 90-day regimen of anti-inflammatory
medications) will be compared to determine whether control of inflammation has an impact on
outcome of intervention for carotid artery stenosis or peripheral arterial disease.
Progress: This protocol remains open to patient entry; however, many of the patients who were
undergoing intervention for carotid artery stenosis or infrainguinal peripheral vascular disease
were already taking high doses of statins (exclusion criteria). Other patients could not wait 30
days prior to the required intervention, which is necessary time for the anti-inflammatory therapy
of statin / ASA to show an effect. Investigators plan to revisit the inclusion criteria and possibly
amend the protocol as necessary to facilitate enrollment.
412
Detail Summary Sheet
Date: 30 Sep 06 Number: 201020 Status: Ongoing
Title: Learning Curves for Airway Assessment and Endotracheal Intubation - Cumulative Sum
Analysis
Principal Investigator: CPT Garth S. Herbert, MC
Department: Surgery/General Surgery Facility: MAMC
Associate Investigator(s): COL Kenneth S. Azarow, MC; LTC Joseph P. Miller, MC; MAJ
James A. Sebesta, MC; CPT James C. Nunley, MC; LTC Gregory P. Fitzharris, MC; CPT Craig
S. See, MC; MAJ Jennifer E. Jorgensen, MC; LTC Ronald J. Place, MC; CPT Jeffrey S Kunz,
MC; LTC Alan L. Beitler, MC; CPT Amy L. Young, DO
Start - Completion: Funding: Periodic Review:
11/28/2000 - Jul 2002 DCI 10/26/2006
Study Objective: (1) To evaluate individual and institutional learning curves for airway
assessment by analyzing diagnostic accuracy as a function of experience for a group of surgical
interns performing a 4-week rotation on the anesthesia service, (2) To develop individual and
institutional learning curves for the skill of endotracheal intubation as a function of experience for
a group of surgical interns performing a 4-week rotation on the anesthesia service, and (3) To
evaluate a model (Cumulative sum analysis) for assessing the technical proficiency of surgical
interns in the skills of airway assessment and endotracheal intubation.
Technical Approach: Surgical interns will receive standardized training on airway anatomy and
assessment coupled with a practical session on intubation in ATLS models. These house officers
will then perform airway assessments and endotracheal intubations on surgical patients who are
18 years or older, ASA class I or II, and who do not require rapid sequence intubation. Each
attempt will be supervised and scored by a staff anesthesiologist or CRNA using a standardized
data sheet. A successful assessment will be one where the airway classification matches the
supervising staffs determination. A successful intubation will be insertion of an endotracheal tube
within 30 seconds of laryngoscopy initiation, documented by end tidal C02. If an attempt is
unsuccessful, the process may be repeated. Each consecutive attempt will be recorded separately.
A data sheet will be filled out and a new score assigned for each attempt, even when there are
multiple attempts on a single patient. Supervising staff will determine if and when they need to
step in and intubate the patients themselves.
Data sheets will be turned in to the principal investigator, who will calculate CUSUM
values and plot learning curves. Data will be monitored during the rotation. At the completion of
the 4-week experience, these results will be shared with the interns and staff. After an entire class
of interns has completed the rotation, the results will be submitted for publication and
presentation.
Progress: This protocol remains ongoing with five additional subjects enrolled during this fiscal
year. Additional efforts were taken to ensure data was retrieved on all surgical interns rotating
through anesthesia, but investigators were not successful in capturing data from all potential
subjects. Data has already been published on the endotracheal intubation portion of the learning
curve assessment. There are no plans to accrue a significant number of subjects to further enhance
the results in this portion of the protocol. Efforts will be focused in the next year towards assessing
the benefit of colonoscopy simulators in preparing interns for real colonoscopies (prepared as an
amendment to this protocol). An associate investigator will be added to assist with data collection
as he is currently working with surgical residents at the Andersen Simulation Center.
413
Detail Summary Sheet
Date: 30 Sep 06 Number: 206027
Status: Ongoing
Title: Prognostic Significance of Telomerase Activity in T1 and T2 Rectal Adenocarcinoma for
Patients Undergoing Transanal Excision
Principal Investigator: CPT Garth S. Herbert, MC
Department: Surgery/General Surgery
Facility: MAMC
Associate Investigator(s): ETC Tommy A. Brown, MC;
COL Kenneth S. Azarow, MC
Start - Completion: Funding:
12/14/2005 - Mar 2006 DCI
Periodic Review:
12/8/2006
Study Objective: To determine the presence and prognostic significance of telomerase activity in
rectal adenocarcinoma for patients who undergo trans-anal excision of these lesions.
Technical Approach: Madigan Army Medical Center operative charts will be reviewed to
identify 20 patients with a diagnosis of rectal adenocarcinoma who have undergone transanal
excision. This data will be coded and immunohistochemistry performed on the paraffin slides of
these tissues. Clinical outcome data will be compared in an attempt to make correlations between
the degree of telomerase activity and pathologic stage, as well as with the incidence of recurrence.
Telomerase activity may prove to be prognostic indicator of which patients should undergo more
aggressive surgery in the management of rectal adenocarcinoma.
Progress: This bench protocol identified fourteen patients who previously underwent trans-anal
excision of rectal cancer. Testing was performed on old surgical specimens. Currently there are
insufficient numbers to determine whether positive staining for telomerase is predictive of
whether tumors will recur. Investigators will attempt to identify other patients who have
undergone transanal excision in order to have sufficient power to determine whether telomerase
staining is a worthwhile procedure in evaluating rectal cancer.
414
Detail Summary Sheet
Date: 30 Sep 06 Number: 205125
Status: Ongoing
Title: Prospective, Randomized, Placebo- Controlled Trial of Tegaserod for Treatment of Delayed
Gastric Emptying after Pancreaticoduodenectomy
Principal Investigator: CPT Garth S. Herbert, MC
Department: Surgery/General Surgery
Facility: MAMC
Associate Investigator(s): ETC Tommy A. Brown, MC;
COL Kenneth S. Azarow, MC
Start - Completion: Funding:
1/9/2006 - Sep 2008 DCI
Periodic Review:
8/28/2006
Study Objective: To determine the efficacy of Tegaserod for relief of delayed gastric emptying
after pancreaticoduodenectomy.
Technical Approach: 70 TRICARE beneficiaries scheduled to undergo pancreaticoduodenectomy
will be asked to enroll. Subjects will be randomized to receive either placebo or Tegaserod 6 mg,
orally, twice a day once oral intake is allowed following pancreaticoduodenectomy. Subjects will be
monitored for evidence of delayed gastric emptying and return of bowel function (flatus, bowel
movements). The time between surgery and discharge will also be recorded. The percentage of
patients in each group with delayed gastric emptying will be compared using the Mann-Whitney
test to determine whether Tegaserod provided any benefit in reducing the incidence of DGE.
Progress: This protocol is open to enrollment, no patients enrolled to date.
415
Detail Summary Sheet
Date: 30 Sep 06 Number: 205126
Status: Ongoing
Title: Prospective, Randomized, Placebo-Controlled Trial of Tegaserod for Treatment of Post-
Operative Ileus Following Partial Colectomy
Principal Investigator: CPT Garth S. Herbert, MC
Department: Surgery/General Surgery
Facility: MAMC
Associate Investigator(s): ETC Tommy A. Brown, MC;
COL Kenneth S. Azarow, MC
Start - Completion: Funding:
1/9/2006 - Sep 2008 DCI
Periodic Review:
9/26/2006
Study Objective: To determine the efficacy of Tegaserod for amelioration of post-operative ileus
following partial colectomy
Technical Approach: 60 TRICARE beneficiaries scheduled to undergo partial colectomy will be
asked to enroll. Subjects will be randomized to receive either placebo or Tegaserod 6 mg orally,
twice a day beginning the day following surgery. Data will be collected on length of hospital stay,
time between surgery and first flatus, first bowel movement, and the time until tolerating a
regular diet. The average hospital stay will be compared between the control and study groups
using the Student's t-test.
Progress: This protocol remains open to patient entry, with eight patients enrolled. One patient
was unblinded due to a concern for anastomotic ischemia prior to being taken back to the
operating room. The patient was found to be on placebo. No analysis will be attempted to date; 7/8
patients remain blinded.
416
Detail Summary Sheet
Date: 30 Sep 06 Number: 205063
Status: Ongoing
Title: The Impact of Nodal Micrometastases on Survival of Women with Breast Cancer
Principal Investigator: CPT Garth S. Herbert, MC
Department: Surgery/General Surgery
Facility: MAMC
Associate Investigator(s): LTC Tommy A. Brown, MC
Start - Completion: Funding:
4/6/2005 - Mar 2006 DCI
Periodic Review:
3/21/2006
Study Objective: To establish whether the presence of nodal micrometastases in breast cancer is
predictive of a worse outcome.
Technical Approach: This study is a retrospective review of all women diagnosed with breast
cancer at MAMC between 1996 and 2003. Survival and disease-free survival will be compared in
patients with benign lymph nodes and those with microscopic evidence of metastasis (tumor foci <
2mm and diagnosed by hematoxylin and eosin stain or immunohistochemistry). Other potential
investigations include (but are not limited to) analysis of the sensitivity of touch prep for analysis
of sentinel lymph nodes at MAMC, and survival in patients with metastasis to the sentinel lymph
node who do or do not have an axillary dissection.
Progress: This retrospective chart review protocol remains ongoing. Over 400 patient charts were
reviewed, but only sixteen patients were identified with isolated tumor cells detected in lymph
nodes. Patient and tumor characteristics, as well as recurrence and survival rates were compared
to women with node negative disease. A difference was not detected in recurrence or survival rates
in patients with isolated tumor cells. Results will be presented at the North Pacific Surgical
Association, and a manuscript is being forwarded to DCI.
417
Detail Summary Sheet
Date: 30 Sep 06 Number: 202073 Status: Terminated
Title: Ultrasound Imaging for Central Venous Catheter Placement in the Intensive Care Unit:
Is Real-time Really Better? A Prospective Randomized Trial
Principal Investigator: CPT Farah A. Husain, MC
Department: Surgery/General Surgery Facility: MAMC
Associate Investigator(s): MAJ Philip S. Mullenix, MC; CPT Michael Piesman, MC; MAJ
Scott R. Steele, MC; LTC Matthew J. Martin, MC; LTC Leonard E. Deal, MC
Start - Completion: Funding: Periodic Review:
10/16/2002 - Dec 2002 DCI 5/24/2005
Study Objective: (1) To compare three methods of internal jugular central venous catheter
placement in a prospective randomized fashion: anatomic landmarks only, ultrasound to evaluate
the anatomy and mark the site, real-time ultrasound guidance. (2) Determine if internal jugular
vein diameter is predictive of successful line placement and/or complications. (3) Analyze cost-
effectiveness of using ultrasound for central line placement. (4) Analyze effect of patient factors
such as age, body mass index, and coagulopathy and prior same-site central lines on successful
central venous catheter placement and complication rate. (5) Analyze effect of operator factors
such as training level, department (medicine, surgery, emergency medicine, etc.) and prior
experience on successful central venous catheter placement and complication rate.
Technical Approach: In this study we will prospectively compare 3 different methods of internal
jugular central venous catheter placement in 100 consecutive patients by random assignment:
anatomic landmarks only, ultrasound to evaluate the anatomy and mark the site, real-time
ultrasound guidance. We will examine data relating to patient factors including age, body mass
index, previous central lines, and coagulopathy. We will also examine procedural data for each
method to include number of needle passes, complications, success or failure of line placement,
time of procedure, and internal jugular vein diameter. There will be no long term or outcome data
studied. The 3 methods will then be compared for any statistically significant difference in ease of
line placement, incidence of complications, and success rates. Data will also be analyzed by
resident year group, experience level, and department of origin. Statistical analysis will be done
using Student's t-test, analysis of variance, and chi-square or Fisher's exact test where
appropriate.
Progress: This study was terminated in September 2006, when the current PI left MAMC and the
remaining study investigators felt continution of the protocol would not be feasible. During the
four years of active study enrollment only 40 of 108 subjects were enrolled. No data analysis was
conducted.
418
Detail Summary Sheet
Date: 30 Sep 06 Number: 206043 Status: Ongoing
Title: Colorectal Complications of External Beam Radiation vs. Brachytherapy for Prostate
Cancer
Principal Investigator: CPT Randy J. Kjorstad, MC
Department: Surgery/General Surgery Facility: MAMC
Associate Investigator(s): LTC Matthew J. Martin, MC; MAJ Philip S. Mullenix, MC; LTC
John B. Halligan, MC; MAJ Scott R. Steele, MC; 2LT Richard N. Lesperance, MC
Start - Completion: Funding: Periodic Review:
1/9/2006 - Feb 2007 DCI N/A
Study Objective: The objective is to determine the prevalence and significance of colorectal
complications (i.e. bleeding, ulceration, proctitis, incontinence) following external beam radiation
therapy versus brachytherapy for prostate cancer.
Technical Approach: A chart review of all cases of each modality will be performed and colon
and rectal complications compared as well as functional outcome for each approach. Records in the
radiation oncology clinic will be used to generate the patient names for each of the two methods.
Data will be collected and organized on an excel spreadsheet for analysis.
Progress: Retrospective data on 288 MAMC patients who received external beam radiation
therapy (EBRT) was collected during FY06. Data analysis is being conducted; although, no
conclusions have been made thus far. Following completion of data analysis, investigators will
decide if it is suitable to proceed with publication with the current number of patients or seek
collaboration with other military treatment facilities, extending the protocol into a multisite study.
419
Detail Summary Sheet
Date: 30 Sep 06 Number: 205127 Status: Terminated
Title: Screening for Occult Vascular Injuries Utilizing a Portable Ultrasound Unit
Principal Investigator: CPT Randy J. Kjorstad, MC
Department: Surgery/General Surgery Facility: MAMC
Associate Investigator(s): CPT Zachary M. Arthurs, MC; CPT Garth S. Herbert, MC; COL
(Ret) Charles A. Andersen, MD; LTC Benjamin W. Starnes, MC
Start - Completion: Funding: Periodic Review:
2/2/2006 - Jul 2007 TATRC via MIPR 8/23/2006
Study Objective: To determine whether a portable ultrasound can be used to identify occult
vascular pathology and the feasibility of using it in a trauma evaluation.
Technical Approach: This will be a biphasic study to first validate a new ultrasound machine
with resident operation on known pathology, then to translate this technology to the trauma
setting. This data will then be compared to reported data on the sensitivity and specificity of color
flow doppler for the diagnosis of vascular pathology. The portable ultrasound utilized in this study
will be a noncommercial machine developed by the staff of Worcester Polytechnic Institute.
Phase I will consist of general surgery and emergency medicine residents utilizing the portable
ultrasound to evaluate ankle-brachial indices and localize segments of vascular disease in patients
with known vascular pathology. Volunteer patients with suspected vascular pathology scheduled
to undergo arteriography will be used in this phase only to validate the portable ultrasound's
accuracy and to develop the resident's skills in identifying pathology. The data gained will be
compared with reported sensitivities and sensitivity of the standard commercially available color
flow Doppler machines ran by trained vascular laboratory technicians.
Phase II will utilize all patients undergoing evaluation of blunt or penetrating extremity trauma
at the emergency room at MAMC. This would consist of an ABI and further ultrasonic
investigation if the ABI<.95. This will be a screening exam only. No clinical decisions will be made
on the information gained from this exam. All findings will be correlated with formal ABI, duplex
ultrasonography, and arteriography if required by current treatment algorithms. The study results
will be compared the published current sensitivity and specificity of color flow doppler in the
diagnosis of vascular injuries to confirm the hypothesis.
Progress: This protocol was terminated due to technical difficulties with the portable ultrasound.
No patients were enrolled in the study.
420
Detail Summary Sheet
Date: 30 Sep 06 Number: 206079 Status: Ongoing
Title: The Utility and Impact of Standard Trauma Triage Criteria in the Elderly
Principal Investigator: LTC Matthew J. Martin, MC
Department: Surgery/General Surgery Facility: MAMC
Associate Investigator(s): CPT Ryan K. Lehmann, MC; CPT Matthew J. Eckert, MC
Start - Completion: Funding: Periodic Review:
4/13/2006 - Oct 2006 DCI N/A
Study Objective: To analyze and compare the trauma triage criteria and implementation as well
as outcomes among elderly (age>65) trauma victims in the State of Washington.
Technical Approach: This is a retrospective study utilizing pooled data collected from several
different hospitals in the State of Washington over a four year period and placed on a database.
Variables pertaining to patient age, length of stay, ICU admission, and trauma scores will be
evaluated for possible trends/correlation between age and outcomes from trauma victims.
Progress: The full database from the Washington State Department of Health has been obtained;
data analysis is planned to begin in December 2006. Preliminary results and an abstract are likely
to be submitted to a national meeting by May 2007. The initial data analysis was delayed due to
the deployment of the primary investigator, but should now proceed as planned.
421
Detail Summary Sheet
Date: 30 Sep 06 Number: 203091 Status: Terminated
Title: Prospective Evaluation Of Intraoperative Duplex Ultrasound As An Adjunct To Technical
Excellence During Carotid Endarterectomy
Principal Investigator: MAJ Philip S. Mullenix, MC
Department: Surgery/General Surgery Facility: MAMC
Associate Investigator(s): COL (Ret) Charles A. Andersen, MD; CPT Zachary M. Arthurs, MC;
CPT Garth S. Herbert, MC; CPT Craig S. See, MC; ETC Benjamin W. Starnes, MC; CPT
Katharine E. Wolcott, MC; CPT Daniel G. Cuadrado, MC; MAJ Scott R. Steele, MC; LTC
Matthew J. Martin, MC; LTC Neal C. Hadro, MC
Start - Completion: Funding: Periodic Review:
7/1/2003 - Dec 2005 DCI 10/14/2005
Study Objective: To prospectively evaluate in an observational fashion the relationship between
intraoperative duplex ultrasound (duplex) findings and subsequent neurologic outcomes and re¬
stenosis rates among patients undergoing carotid endarterectomy (CEA). To prospectively evaluate
in an observational fashion our duplex criteria for immediate revision of endarterectomy.
Technical Approach: This is an observational prospective cohort study designed to evaluate the
relationship between intraoperative duplex ultrasound findings and subsequent neurologic
outcomes and re-stenosis rates among 120 patients undergoing carotid endarterectomy, and to
prospectively evaluate our duplex criteria for immediate revision of endarterectomy. The study
represents no deviation from the current standard of care at this facility and involves no additional
procedures, medications, or interventions above that already being provided as part of the
treatment of the patient's disease process.
Progress: This protocol was terminated by the PI in June 2006, with no subjects enrolled.
Initiation of the protocol was not possible due to time contraints.
422
Detail Summary Sheet
Date: 30 Sep 06 Number: 206061 Status: Ongoing
Title: Utilization of Genetic Testing and Counseling Among Patients with Hereditary Non-
Polyposis Colorectal Cancer
Principal Investigator: CPT Jason T. Perry, MC
Department: Surgery/General Surgery Facility: MAMC
Associate Investigator(s): LTC Tommy A. Brown, MC
Start - Completion: Funding: Periodic Review:
2/7/2006 - Jul 2006 DCI N/A
Study Objective: To describe rates of utilization of genetic testing and counseling (GTC) among
patients diagnosed with hereditary non-polyposis colorectal cancer (HNPCC) and further
characterize use of recommended screening/surveillance studies after receiving GTC.
Technical Approach: Patients contained in the Madigan colorectal cancer database (from its
inception in 1995 to present) and meeting the Amsterdam criteria II criteria will be extracted. The
uptake of genetic testing and counseling will then be derived by reviewing patient medical records
(including pathology results contained within the CHCS), and patient records from Medical
Genetics. This study will further attempt to characterize patients' adherence to recommended
screening guidelines and or surgical interventions follow testing and counseling in comparison to
patients that did not accept testing or counseling.
Progress: This protocol is still in the data acquisition phase and no conclusions are available at
this time.
423
Detail Summary Sheet
Date: 30 Sep 06 Number: 206038 Status: Ongoing
Title: Venous Distensibility Index as a Predictor of Radiocephalic Arteriovenous Fistula
Maturation
Principal Investigator: CPT Jason T. Perry, MC
Department: Surgery/General Surgery Facility: MAMC
Associate Investigator(s): COL (Ret) Charles A. Andersen, MD; LTC Benjamin W. Starnes,
MC; COL Howard M. Cushner, MC
Start - Completion: Funding: Periodic Review:
1/5/2006 - Jul 2006 DCI N/A
Study Objective: Objective is to determine whether venous compliance, as measured by a venous
distensibility index (VDI), is associated with an increased rate of arteriovenous fistula (AVF)
maturation.
Technical Approach: 50 patients with end-stage renal disease referred to Vascular Surgery for
consideration of permanent hemodialysis vascular access will be offered enrollment in this study.
Venous distensibility index will be determined by modifying the preoperative ultrasound protocol
already utilized in every dialysis candidate in whom an arteriovenous fistula is considered. In
addition to collecting historic (e.g. duration and etiology of end-stage renal disease), physiologic
(creatinine clearance, HbAlc), morphologic data (vein calibers, venous distensibility index),
patients will be followed to determine the rate of maturation at six weeks and three and six
months post-operatively. Maturation rate at three months will be considered the primary endpoint
with maturation rates at six weeks and six months and fistula volume flow and arterial and
venous wall thicknesses at one and six weeks and three and six months considered secondary
endpoints. At this time, the data will be analyzed to determine whether a cutoff VDI can be
established which segregates patients into mature versus failure to mature groups. Chi-square
analysis or Fisher's exact test will be used to compare the groups.
Progress: This protocol remains open to patient entry, with five patients enrolled during FY06.
Data collection continues.
424
Detail Summary Sheet
Date: 30 Sep 06 Number: 206116 Status: Ongoing
Title: Breast Papillomas in the Era of Stereotactic Core Biopsy
Principal Investigator: CPT Vance Y. Sohn, MC
Department: Surgery/General Surgery Facility: MAMC
Associate Investigator(s): LTC Tommy A. Brown, MC; CPT Joren B. Keylock, MC
Start - Completion: Funding: Periodic Review:
8/15/2006 - Dec 2006 DCI N/A
Study Objective: To determine natural history of breast papillomas diagnosed during core needle
biopsy.
Technical Approach: This will be a retrospective chart review of all patients with a diagnosis of
papilloma on core needle biopsy. Data will be further analyzed with follow-up radiographic and
other clinical notes. Those patients who underwent excisional biopsy will be compared to those
who did not undergo immediate biopsy, but were rather follow-up serially with radiographs.
Progress: From January 1994 until December 2005, 5,257 stereotactic core needle biopsies
(SCNB) were performed at our tertiary level medical center; 206 patients were diagnosed with 215
breast papillomas; 172 (80%) papillomas were benign, 25 (12%) were associated with atypia, and
15 (7%) were associated with malignancy. Three benign papillomas (1.7%) developed into cancer (1
infiltrating ductal carcinoma, 2 ductal carcinoma in-situ) over an average of 44 months. Average
follow-up of those patients not undergoing excision for benign papilloma was 41 months, although
we had 92 patients with greater than 2 year follow-up and 57 patients with greater than 4 year
follow-up. Of patients with atypia or malignancy associated with papilloma, there was a 26% and
87% associated rate of malignancy, respectively. This protocol remains ongoing for continued data
analysis and completion of final paper.
425
Detail Summary Sheet
Date: 30 Sep 06 Number: 206114
Status: Ongoing
Title: Institutional Accuracy of 11- and 8- Gauge Vacuum-Assisted Core Biopsy of
Mammographic Breast Lesions
Principal Investigator: CPT Vance Y. Sohn, MC
Department: Surgery/General Surgery
Facility: MAMC
Associate Investigator(s): LTC Tommy A. Brown, MC
Start - Completion: Funding:
8/8/2006 - Dec 2007 DCI
Periodic Review:
N/A
Study Objective: To determine the accuracy of 11 and 8 gauge core needle sterotactic vacuum-
assisted needle biopsy.
Technical Approach: A review of Breast pathway charts will be completed to identify patients
with a diagnosis of atypical ductal hyperplasia on core biopsy who went on to open surgical biopsy.
Of these, patients will be selected with a subsequent diagnosis of DCIS or invasive carcinoma and
stratified according to the mammotome gauge. Correlation and analysis will be performed to see
the accuracy of diagnosis of the 11 and 8 gauge mammotome between core needle biopsy and final
excisional surgical biopsy. Results will be compared to published surgical literature.
Progress: The protocol remains ongoing for continued data analysis and completion of final paper.
From June 1996 until July 2006, 4,579 stereotactic core needle biopsies (SCNB) were performed at
our tertiary level medical facility; 78 of 88 (89%) of patients diagnosed with ADH on SCNB with an
11-gauge vacuum-assisted needle underwent open surgical excision. Of these patients, nine (11%)
were upgraded to ductal carcinoma in-situ (DCIS) while five (6%) had infiltrating ductal carcinoma
(IDC) for a total underestimation rate of 17%. These results differ from our previously published
series of 14-gauge SCNB which revealed an underestimation rate of 36%. Mean age of our patients
was 58 years, with 71 (82%) undergoing percutaneous biopsy for microcalcifications discovered on
routine mammography. Most common excisional diagnosis was focal ADH or atypical lobular
hyperplasia (ALH) in 44 (56%) patients. Mean number of passes obtained at time of biopsy, mean
age of patients, and characteristic radiographic abnormality were similar for malignant and
benign diagnosis.
426
Detail Summary Sheet
Date: 30 Sep 06 Number: 206004
Status: Ongoing
Title: The Evaluation of Telomerase Inhibition in a Colorectal Metastasis Model Using Nude
Mice (Mus musculus)
Principal Investigator: CPT Vance Y. Sohn, MC
Department: Surgery/General Surgery
Facility: MAMC
Associate Investigator(s): ETC Tommy A. Brown, MC;
Jason T. Perry, MC; CPT Garth S. Herbert, MC
COL Kenneth S. Azarow, MC; CPT
Start - Completion: Funding:
11/8/2005 - Oct 2008 DCI
Periodic Review:
N/A
Study Objective: This study will test imatinib mesylate in vivo to determine its efficacy in
limiting metastatic spread of human colon cancer in nude mice.
Technical Approach: Experiment 1
A pilot study will be conducted to validate the method of delivery of tumor cells. Mice will be
anesthetized under standard policy as per the MAMC veterinarian. 26 mice will be used, 13 in
each group. A mini-laparotomy will be performed and the spleen mobilized. Approximately 4
million colon cancer cells suspended in saline vs. saline alone will be injected into the subcapsular
space of the spleen using a 26 gauge needle. After 10 minutes, the splenic vessels will be ligated,
and the spleen removed. The abdominal incision will then be closed using simple interrupted
sutures of 4.0 Vicryl. The animals will then be returned to their cages, which will be maintained at
90oF until animals have recovered fully from anesthesia. They will be allowed food and water ad
lib. All mice will be observed for evidence of study endpoints. All surviving mice will be sacrificed
at 60 days following surgery. The liver will be removed, and weighed in order to quantify the
extent of metastatic spread. Data from mice who had saline alone injected into the spleen will be
used establish a baseline liver weight. The percentage of mice surviving, as well as the length of
time required for appreciable tumor growth may dictate modification of these factors in
subsequent experiments.
Experiment 2
After verifying that the above model of tumor metastasis functions effectively, we will begin the
second arm of the study. Mice will undergo the same procedure as detailed above. We intend on
using 13 mice per group, although survival results and tumor size in Experiment 2 may require
modifications. One half of the mice will then be administered imatinib mesylate (lOmg/kg/day)
orally (gavage), while mice in the control group will receive saline gavage. Again, the animals will
be allowed food and water ad lib. All mice will be observed daily, watching for study endpoints as
detailed in V.4.5. All surviving mice will be sacrificed at 60 days following surgery. The liver will
be removed, and weighed in order to quantify the extent of metastatic spread. The mass of the
liver will be compared between the two groups to quantify the ability of imatinib mesylate to
inhibit metastatic spread of colon cancer. In addition, portions of the liver will also be frozen for
subsequent quantification of telomerase activity.
Experiment 3
Additional experiments using the model established above will be conducted using other
telomerase inhibitors, as compared to imatinib mesylate, or in conjunction with established anti¬
neoplastic agents with efficacy against colon cancer, such as 5-fluorouracil, irinotecan,
capecitabine and bevacizumab. Again, based on preliminary power analysis, 13 animals will be
required per group (with approximately 8 groups to include a control group, an imatinib only
group, and multiple groups that receive other antineoplastic agents with or without imatinib).
427
Progress: The plan was for a multi-armed procedure using mice. During the first pilot study, a
power analysis was performed after completion as described in the original protocol in which the
numbers required to proceed was greater than 40,000 mice. Therefore, a repeat pilot was
performed. This too however was unsuccessful. We are currently reviewing the literature to
determine the technical aspects to continue with this protocol.
428
Detail Summary Sheets
Ophthalmology Service, Department of
Surgery
429
Detail Summary Sheet
Date: 30 Sep 06 Number: 204085
Status: Completed
Title: Flow Cytometry Descriptive Findings from Lacrimal Sac Biopsy Specimens, Obtained in
Standard Dacryocystorhinostomy
Principal Investigator: LTC Darryl J. Ainbinder, MC
Department: Surgery/Ophthalmology Surgery
Facility: MAMC
Associate Investigator(s): COL Jerome B. Myers, MC;
A. Mazzoli, MC; CPT Kerry L. O’Brien, MC
CPT Travis C Frazier, MC; COL Robert
Start - Completion: Funding:
6/16/2004 - May 2005 DCI
Periodic Review:
5/22/2005
Study Objective: This study will provide a descriptive baseline of the flow cytometry findings
from lacrimal sac biopsy specimens obtained in standard dacryocystorhinostomy.
Technical Approach: Investigators will conduct a prospective descriptive study of the flow
cytometric features, of tissue specimens obtained during standard dacryocystorhinostomy surgery,
in adults. These tissue specimens currently receive standard histopathologic evaluation. The
study plans to enroll a maximum of 50 patients from two staff oculoplastic surgeons who present
to the Ophthalmology Service for symptoms of chronic dacryocystitis and adult nasolacrimal duct
obstruction. On histopathology, the overwhelming tissue diagnosis is chronic inflammation of the
lacrimal sac. Demographic data will be collected and clinical findings reported on standard
oculoplastic history and physical examination sheet. Only one study provider will transfer the
clinical data onto a numeric study database. Raw data and flow cytometry descriptive reports will
be collected, as well as the histopathologic final tissue diagnosis. The data collection process will be
numerically coded with no patient protected health or identifying information in the database. At
the end of one year data collection will be discontinued. Investigators will review and present the
flow cytometric features of patients undergoing standard dacryocystorhinostomy. The final tissue
histopathology will allow correlation with flow cytometric findings to tissue histopathology. The
demographic and clinical data will allow characterization of basic features of the study clinical
population.
Progress: This protocol was reported completed in May 2006, with six patients enrolled in the last
twelve months for a total enrollment of nine. The descriptive findings on flow cytometry
demonstrated a consistent description of the sub mucosal chronic inflammatory infiltrate found on
histopathology of standard patients undergoing dacryocystorhinostomy for nasolacrimal duct
obstruction. Flow cytometry demonstrates a mixed population of phenotypically normal B and T
cells. There has been no evidence of light chain restriction. These findings help to build a
descriptive baseline of flow cytometry results in patients with obstruction who do not have
confounding malignancy or granulomatous disease.
430
Detail Summary Sheet
Date: 30 Sep 06 Number: 206076
Status: Completed
Title: Methicillin Resistant Ascending Facial and Orbital Cellulitis
Troop Population
in Operation Iraqi Freedom
Principal Investigator: CPT John H. Boden, MC
Department: Surgery/Ophthalmology Surgery
Facility: MAMC
Associate Investigator(s): LTC Darryl J. Ainbinder, MC
Start - Completion: Funding:
4/6/2006 - Dec 2006 DCI
Periodic Review:
N/A
Study Objective: (1) To present a descriptive case series of methicillin resistant ascending facial
and orbital cellulitis in Operation Iraqi Freedom (OIF) troop population. (2) To make aware that
methicillin resistance must be considered in rapidly progressive skin and soft tissue infections in
active duty troop population. Occult, resistant, nasal infections may be the source for ascending
orbital cellulitis.
Technical Approach: Physician will transfer summaries of patients cared for and treated by Col
Ainbinder while serving in Operation Iraqi Freedom for review. Patients with MRSA facial
cellulitis from a peri-nasal or nasal mucosal source will be evaluated. Of those, cases which
demonstrated ascending progression to peri-orbital, or orbital cellulitis will be included in this
review.
Progress: In a retrospective review of MRSA isolates obtained at an Army community hospital,
the prevalence of MRSA isolates increased from 12% in 1998 to 43% in 2003. This study also
demonstrated that over a five year period, 93% of MRSA isolates were cultured from out-patients
without any risk factors for hospital-associated MRSA. This study presented five cases of
aggressive ascending facial cellulitis with peri-orbital or orbital cellulitis from a nasal mucosal
source. None of the cases had CT or clinical evidence of a sinus source of infection. It is important
to note that in every case, the patient assumed that the small abscess inside the mares was not
related to their illness. None of the patients complained of nasal pain until nasal inspection with a
speculum was performed. Nasal cultures demonstrated MRSA and greatly assisted in the
treatment of each patient. It is imperative that the treating physician be cognizant of the
increasing prevalence of MRSA infections and be aware that a superficial nasal MRSA infection
can progress to orbital cellulitis, meningitis, and possibly death. The nasal source can be occult
due to the distracting presentation of the orbit and systemic findings. These patients look sick, and
the proptotic globe changes are striking. It is imperative to examine, culture, drain wounds from
the nose in patients presenting with peri-orbital or orbital cellulitis so that a nasal follicular
abscess will not be overlooked.
431
_ Detail Summary Sheet _
Date: 30 Sep 06 Number: 206124 Status: Ongoing
Title: The use of lidocaine gel prior to povidone - iodine antisepsis and its effect on microbial
survivability
Principal Investigator: CPT John H. Boden, MC
Department: Surgery/Ophthalmology Surgery Facility: MAMC
Associate Investigator(s): LTC Mark F. Torres, MC; CPT David M. Bushley, MC
Start - Completion: Funding: Periodic Review:
9/21/2006 - Oct 2006 DCI N/A
Study Objective: To determine if the use of lidocaine gel prior to povidone-iodine antisepsis
caries an increased risk of microbial survivability
Technical Approach: 1. A standard 0.5 McFarland suspension of Staphylococcus epidermidis
will be diluted 1:10 with normal saline. A 0.001 ml loop will be used to inoculate each plate to give
a standard 1 x 104 to 1x105 colony forming units on each blood agar plate.
2. A control group of 5 blood agar plates will be inoculated and labeled
3. A group of 5 plates of inoculated blood agar will have lidocaine gel applied to the plate. The
lidocaine gel will be allowed to drip across the agar plate as the plate is held vertically. After the
lidocaine gel has covered the entire plate, the excess lidocaine gel will be wiped out using a sterile
cotton tip applicator, and the plate will be stored upside down so that residual lidocaine gel can
continue to drop off the agar plate. Each plate will be labeled.
4. A group of 5 inoculated blood agar plates will have lidocaine gel applied to the plate in the same
manner as step 3. The plate will be placed upside down to allow excess gel to drip off the plate for
5 minutes. Dilute povidone-iodine 5% ophthalmic solution will be placed onto agar plate so that is
covers the plate. The povidone-iodine solution will be left in place for 30 seconds and then the
residual povidone-iodine solution will be dumped out of the agar plate. Each plate will be labeled.
5. A group of 5 plates of inoculated blood agar will have dilute povidone-iodine 5% ophthalmic
solution placed onto agar plate and allowed to cover the plate for 30 seconds. After 30 seconds the
povidone-iodine solution will be dumped out of the agar plate. Each plate will be labeled.
6. Steps 1 through 5 will be repeated 3 more times, but instead of using Staphylococcus
epidermidis, staphylococcus aureus, Pseudomonas aeruginosa and Haemophilus influenzae will be
used in each reiteration respectively. When Haemophilus influenzae is used standard chocolate
agar will be used instead of blood agar.
7. The plates will be placed in a standard microbiology incubator used for aerobic culture, and
microbial growth will be evaluated 24 hours later. If there is no growth after 24 hours, the plates
will be reevaluated after another 24 hour time
Progress: This minimal risk protocol received initial approval by the Expedited Review
Committee, effective 20 September 2006.
432
_ Detail Summary Sheet _
Date: 30 Sep 06 Number: 206006 Status: Ongoing
Title: Virtual Ophthalmosurgical Simulator as a Valid Training Tool
Principal Investigator: CPT Daniel J. Solverson, MC
Department: Surgery/Ophthalmology Surgery Facility: MAMC
Associate Investigator(s): COL Robert A. Mazzoli, MC; LTC William R. Raymond IV, MC;
LTC Mark L. Nelson, MC; COL Kenneth S. Azarow, MC; COL Craig D. Hartranft, MC
Start - Completion: Funding: Periodic Review:
10/21/2005 - Feb 2006 DCI 9/21/2006
Study Objective: To establish the validity of an ophthalmosurgical virtual reality simulator for
intraocular surgery as an educational and assessment apparatus.
Technical Approach: All medical students, residents, ophthalmology staff physicians willing to
participate will be recruited, have a visual acuity exam and be asked to complete a questionnaire
to assess level of experience regarding microsurgery and handedness. All subjects will receive
specific instructions on how to perform a navigation task on the EYE SI virtual reality simulator by
watching an instructional videotape. Each participant will complete several tasks including
arranging small spheres near the retina and peeling a membrane off the retina. Main outcome
measures in the arrangement task will be time to complete task as well as time to first error (such
as a retinal hit) and participant microtremor throughout task. Each participant will also
consecutively perform each task for a total of 15 times. Time intervals will be recorded between
each consecutive task. Evaluations include: the relationship between the surgical experience and
the task's completing time using ANOVA; the relationship between stereopsis and the task's
completion time using Pearson correlation test; and the relationship between the surgical
experience and the average tremor score using Pearson correlation test. To study the learning
curve, the consecutive completion times for each subject and ANOVA will be evaluated to
determine if there was a significant decrease in completion time throughout the 15 trials. For the
membrane peeling task, the relationship between surgical experience and stereopsis with the
number of retinal contacts, the task's completion time, and average tremor using ANOVA or
Pearson correlation test will be evaluated, as appropriate.
Progress: This protocol remains open to enrollment, with 35 subjects entered who have
undergone the testing on the virtual reality simulator. Comparing expert and novice surgeon
performance on same task, preliminary data shows that expert surgeons showed a greater facility
with microsurgical tasks, but with repeated practice, novice surgeons showed improvement in all
performance scores.
433
Detail Summary Sheet
Date: 30 Sep 06 Number: 204049
Status: Completed
Title: Long-Term Follow-up of Military Personnel Following Photorefractive Keratectomy With
Mitomycin-C
Principal Investigator: LTC Mark F. Torres, MC
Department: Surgery/Ophthalmology Surgery
Facility: MAMC
Associate Investigator(s): CPT Roger A. Anderson, MC;
Adam G. Buchanan, MC
CPT Steven J. Rogers, MC; CPT
Start - Completion: Funding:
3/17/2004 - Mar 2004 DCI
Periodic Review:
3/22/2005
Study Objective: (1) To determine the effect of mitomycin-c on post-operative refraction when it
is used in Photorefractive Keratectomy (PRK). (2) To assess for the presence of corneal haze
following Photorefractive Keratectomy with mitomycin-c.
Technical Approach: A retrospective chart review will be conducted on all subjects who have
undergone Photorefractive Keratectomy with Mitomycin-c at the Madigan Refractive Surgery
Center. The study will include approximately 20-30 subjects in the 18-50 year old age range. The
final number of subjects will depend on how many meet entry criteria at the time the study is
initiated. For each chart reviewed data will be recorded on subject's pre-operative and
postoperative vision and refraction (spectacle prescription) and comparing the actual results
(paired t-test) to the predicted values. The presence or absence of postoperative corneal haze,
wound recidivism, will also be assessed. A protocol revision expanded the chart review to include
all patients undergoing PRK with adjunctive use of mitomycin C through Jan 05. The number of
charts planned to reviewed was updated to 30 to 50.
Progress: Although an amendment to the protocol was approved in April 2005, no study activity
occurred during that fiscal year or in fiscal year 2006. This study is completed at MAMC.
434
Detail Summary Sheet
Date: 30 Sep 06 Number: 205083
Status: Ongoing
Title: Ophthalmic Phentolamine Multiple Dose Clinical Trial
Principal Investigator: LTC Mark F. Torres, MC
Department: Surgery/Ophthalmology Surgery
Facility: MAMC
Associate Investigator(s): CPT Aaron G. Amacher, MC
Start - Completion: Funding:
11/17/2005 - Apr 2005 Ocularis Pharma via The Geneva Foundation
Periodic Review:
6/7/2006
Study Objective: Determine the effect on pupillary diameter of multiple doses of ophthalmic
phentolamine (OP). Determine the effect on contrast sensitivity, glare sensitivity, and visual
acuity of multiple doses of (OP). Determine the subjective benefits of multiple doses of OP.
Determine the onset of action, the time of peak effect and the duration of the response of OP
following multiple doses. Determine the safety and tolerability of OP following multiple doses.
Technical Approach: The Ophthalmic Phentolamine (OP) Multiple Dose Clinical Trial will study
12 otherwise healthy, 21-55 year old men and women who have had refractive surgery and have
post surgical complaints of night vision problems. The study will be a randomized double-blinded
placebo controlled crossover study with two periods. Each patient will receive two of three possible
treatments: placebo, 0.2%, or 0.4% phentolamine. Pupil size, contrast sensitivity, glare sensitivity,
accommodation, blood pressure and heart rate will be measured prior to application of OP.
Following OP administration these variables will again be measured at intervals of one, four, and
eight hours. Pre- and post-OP administered pupillary size, contrast sensitivity, visual acuity, glare
sensitivity, subjective assessments, blood pressures and heart rates will be statistically compared
in order to: (1) Determine the effect on pupillary diameter of multiple doses of ophthalmic
phentolamine (OP). (2) Determine the effect on contrast sensitivity, glare sensitivity, and visual
acuity of multiple doses of (OP). (3) Determine the subjective benefits of multiple doses of OP. (4)
Determine the onset of action, the time of peak effect and the duration of the response of OP
following multiple doses. (5) Determine the safety and tolerability of OP following multiple doses.
Progress: This protocol remains open to enrollment, but no glare patients have yet been
identified. Recruitment continues.
435
Detail Summary Sheets
Orthopedics Service, Department of Surgery
436
Detail Summary Sheet
Date: 30 Sep 06 Number: 206022 Status: Ongoing
Title: Accuracy of Reduction Utilizing Volar Fixation for Dorsally Displaced Fractures of the
Distal Radius
Principal Investigator: CPT Ivan J. Antosh, MC
Department: Surgery/Orthopedic Surgery Facility: MAMC
Associate Investigator(s): CPT Joshua P. Herzog, MC; COL Sean D. Ghidella, MC; LTC John
G. DeVine, MC; CPT Llewellyn V. Lee, MC
Start - Completion: Funding: Periodic Review:
2/8/2006 - Nov 2006 DCI 10/26/2006
Study Objective: To determine the accuracy of a volar fixed angle plate in operatively treated
distal radius fractures.
Technical Approach: This study will enroll the next 34 patients that present with a distal radius
fracture who are selected by the treating physician to undergo surgical correction with a Hand
Innovations DVR plate. All patients will undergo a preoperative and postoperative CT scan of their
wrist. There will be no change in the operative approach, surgical technique or postoperative
rehabilitation. Demographic and contact information will be gathered.
Radiographic measurements of the injury CT and post-op CT will be evaluated by three separate
readers and the averages used for statistical calculations. The films will be evaluated for (1) radial
height, (2) radial inclination (3) dorsal/volar angulation (4) articular step-off (5) articular gapping
(6) degree of comminution using a visual analog scale, (7) presence or absence of distal radioulnar
joint (DRUJ). The preoperative measurements will then be compared to the postoperative
measurements utilizing the paired student T-test. The data from this study will be used to predict
the accuracy of reduction with utilization of the Hand Innovations DVR plate.
Progress: Due to scheduling and time constraints, no patients were enrolled during FY06.
Investigators plan to begin subject enrollment in November 2006.
437
Detail Summary Sheet
Date: 30 Sep 06 Number: 206037 Status: Ongoing
Title: A Retrospective Review of Injuries Sustained During Operation Iraq Freedom and
Operation Enduring Freedom Requiring Medical Evacuation to a Tertiary Medical Center
Principal Investigator: COL Edward D. Arrington, MC
Department: Surgery/Orthopedic Surgery Facility: MAMC
Associate Investigator(s): CPT Joshua P. Herzog, MC; CPT John A. Guzzo, MC; LTC John G.
DeVine, MC
Start - Completion: Funding: Periodic Review:
12/21/2005 - Mar 2006 DCI 12/8/2006
Study Objective: To provide an expanded casualty survey of evacuations to an Army Medical
Center over the past 22 months via a retrospective chart review.
Technical Approach: Utilizing the daily OIF/OEF patient diagnosis report from Jan 2003-Nov
2005 approximately 1085 soldier who were evacuated from OIF/OEF have been identified. A
retrospective chart review using CIS, ICDB, ORMA and Dinpacs will be conducted. Demographic
data to include age, sex, MOS and military rank will be collected. The patient diagnosis report and
the detailed chart review will be used to document the type of injuries (Fracture, Neuro/vascular
Damage, Amputation, Wound Care, Overuse Syndromes, Ligament Damage), Location of Injuries
(Hand, Forearm, Arm, Shoulder, Foot, Leg/Ankle, Femur, Hip, Pelvis, Spine), Disease Non-Battle
Injury vs. Combat Injury, Treatments, Number of days from injury, Pre-existing condition. Army
Personnel Command will also be contacted to determine the normal demographical data for
deploying soldiers out of the Pacific Northwest. This data will then be compared to the med-evac
patient population to evaluate for a statistical difference. The data will be further evaluated by
graphical means.
Progress: This is a retrospective review of patients with injuries sustained during Operation Iraq
Freedom (OIF) and Operation Enduring Freedom (OEF) who required medical evacuation to
Madigan Army Medical Center. Data collection was completed during FY06; data analysis had
begun.
438
Detail Summary Sheet
Date: 30 Sep 06 Number: 201015 Status: Ongoing
Title: Biomechanics of Various Coracoclavicular Ligament Reconstruction Techniques
Principal Investigator: COL Edward D. Arrington, MC
Department: Surgery/Orthopedic Surgery Facility: MAMC
Associate Investigator(s): CPT Kurtis L. Kowalski, MC; COL (Ret) Patrick St Pierre, MD;
CPT Brendon R. Connolly, MC; MAJ Paul M. Ryan, MC; MAJ Creighton C. Tubb, MC; CPT
Wendy J. Boucher, MC; CPT Joshua P. Herzog, MC
Start - Completion: Funding: Periodic Review:
11/15/2000 - Dec 2004 Mitek via Proffer 9/21/2006
Study Objective: Test the strength and biomechanical characteristics of native and intact
coracoclavicular ligament complexes as well as various reconstructive techniques for treating high-
grade acromioclavicular joint separations.
Technical Approach: Thirty coracoclavicular bone-ligament-bone specimens will be harvested
from fresh-frozen human cadavers. Unidirectional tensile loading will be performed with the
Instron device. Tensile loading will be applied to the clavicle at a uniform rate until failure of the
coracoclavicular ligament complex occurs. The coracoclavicular ligament will then be reconstructed
using gracilis tendon, palmaris longus tendon, or SIS graft. The grafts will be looped multiple
times under the coracoid process and over the top of the clavicle. It will be secured to itself with a
#2 Ethibond suture. They will then be tested to failure as previously described.
Data will be obtained from the Instron device regarding tensile strength, load to failure, stiffness,
and elongation to failure. Statistical analysis will be performed using a one-way ANOVA to
determine differences between groups as well as Duncan's multiple range test to determine
specific differences.
Progress: This bench protocol remains ongoing. Since initiation, numerous cadaver matched
shoulders have been tested, both controls and experimentals. The data appears to be good and
reproducible. Statistical analysis continues to determine what the next step needs to be, including
the testing of additional matched controls and refinement of Instron techniques. Investigators
have also begun testing additional experimental reconstructions.
439
Detail Summary Sheet
Date: 30 Sep 06 Number: 204051 Status: Ongoing
Title: Efficacy of Post-operative Hip Spica Wrap Dressing after Primary Hip Arthroplasty in
Preventing Post-operative Wound Complications and Blood Transfusions
Principal Investigator: COL Edward D. Arrington, MC
Department: Surgery/Orthopedic Surgery Facility: MAMC
Associate Investigator(s): CPT Aaron H. Hoblet, MC; MAJ James A. Hall, MC; CPT John J.
McGuigan, MC; CPT Nathan T Boykin, MC
Start - Completion: Funding: Periodic Review:
9/8/2004 - July 2004 DCI 2/22/2006
Study Objective: To determine the efficacy of post-operative hip spica wrap dressing in primary
hip arthroplasty in preventing wound complications and blood transfusions.
Technical Approach: Patients undergoing total hip arthroplasty or hemi-arthroplasty, electively
or due to trauma, over the age of 18, male or female, are eligible to participate in this study. The
next 20 patients who meet inclusion criteria will be randomly selected, after wound closure, to be
placed in group A (standard wound closure with standard dressing and paper tape plus a hip spica
wrap dressing) or Group B (the control group, standard wound closure with standard dressing of
perforated cloth tape without the hip spica wound dressing). Data will be recorded pre-operatively
to include medical comorbidities, height, weight, pre-albumin, albumin, hematocrit and post-
operatively to include length of incision, amount of drainage per dressing, weight, the change in
hematocrit, the need for a transfusion, length of hospital stay and any wound complications. Using
the Student's T-test, this study will show a statistically significant decrease in wound drainage,
decreased number of wound complications, decrease in length of hospital stay, smaller drop in the
hematocrit and decrease need for transfusions.
Progress: This protocol has not been initiated awaiting an orthopaedic research coordinator to
facilitate data collection and a total joint surgeon to be in place to enroll potential subjects.
440
Detail Summary Sheet
Date: 30 Sep 06 Number: 203036 Status: Ongoing
Title: Intramedullary Fixation of Displaced Acute Middle One-Third Clavicle Fractures
Principal Investigator: COL Edward D. Arrington, MC
Department: Surgery/Orthopedic Surgery Facility: MAMC
Associate Investigator(s): MAJ Karin A. Johnson, MC; CPT John J. McGuigan, MC; Steven D.
Travers, MPT; ETC Craig R. Bottom, MC; MAJ Eric L. Smith, MC
Start - Completion: Funding: Periodic Review:
3/18/2003 - Mar 2005 DCI 1/24/2006
Study Objective: To determine the usefulness of intramedullary fixation of the treatment of
100% displaced middle one-third clavicle fractures. Compare the rates of union, nonunion, and
malunion versus non-operative treatment.
Technical Approach: This study will randomize patients with acute displaced middle one-third
clavicle fractures to either standard non-operative treatment or to open reduction and
intramedullary pin fixation. The ultimate goal of this research is to obtain fracture healing with
anatomic alignment, in order to promote an earlier return to full duty using a minimally invasive
method of fracture stabilization. If successful, normal shoulder mobility and function will be
restored faster and the patients can return to full activities sooner.
Progress: This protocol continues to actively recruit subjects. Since initiation, fifteen subjects
have enrolled, six during FY06. No complications or adverse events have occurred.
441
Detail Summary Sheet
Date: 30 Sep 06 Number: 206085 Status: Ongoing
Title: Pectoralis Major Repairs in Active Duty Soldiers
Principal Investigator: COL Edward D. Arrington, MC
Department: Surgery/Orthopedic Surgery Facility: MAMC
Associate Investigator(s): CPT Jason A. Grassbaugh, MC; CPT Ivan J. Antosh, MC; LTC John
G. DeVine, MC
Start - Completion: Funding: Periodic Review:
5/8/2006 - Mar 2007 DCI N/A
Study Objective: A retrospective review of all pectoralis major repairs performed at Madigan
Army Medical Center from 2000 to 2006 with an objective to define expected results in terms of
strength, functionality, pain, and ability to return to work among the active duty population.
Technical Approach: A list of all active duty soldiers who underwent operative repair of
pectoralis major tendon tears from 2000-2006 will be gathered from operative records. Chart
review will be performed in order to ascertain date of surgery, operative findings, repair
methodology, rehabilitative plan and follow up visitations. After obtaining this data, patients will
be contacted in writing in order to complete the DASH (Disability in arm, shoulder, and hand
questionnaire). Results will be accumulated and analyzed.
Progress: This is a retrospective review of the functional outcome of pectoralis major rupture
repairs in active duty Soldiers. Fifteen patients treated over the past four years at MAMC have
been contacted during FY06. Information has been returned from thirteen patients. The protocol
remains ongoing to conduct data analysis.
442
Detail Summary Sheet
Date: 30 Sep 06 Number: 206036
Status: Ongoing
Title: Return to Full Duty after Anterior Cruciate Ligament Reconstruction
Population
in the Military
Principal Investigator: COL Edward D. Arrington, MC
Department: Surgery/Orthopedic Surgery
Facility: MAMC
Associate Investigator(s): LTC John G. DeVine, MC; CPT Joshua P. Herzog, MC
Start - Completion: Funding:
12/20/2005 - Jun 2006 DCI
Periodic Review:
12/8/2006
Study Objective: Objectives are to determine the rate of return to a soldier's pre-injury MOS
after undergoing an anterior cruciate ligament (ACL) reconstruction and to identify risk factors to
assist in predicting a decrease rate of return to full duty.
Technical Approach: A retrospective chart review of all 604 active duty patients who underwent
an ACL reconstruction from 1994-2002 will be performed to identify potential predictors of poor
outcomes, such as Age, Gender, MOS, time from injury to surgery, graft choice, intra- articular
injuries (meniscal tear, meniscal treatment, chondral injuries, chondral treatment), duration of
follow-up. Patients will be mailed questionnaires that will include four validated outcome
instruments, a review of systems, questions regarding additional surgery, questions regarding any
changes in social or demographic information. Patients will be asked what their pre-injury MOS
was and if this was maintained post-rehabilitation (6 months); their current occupation; if they
have ever undergone an MEB and the underlying condition that generated the MEB, and if they
have a permanent profile for symptoms related to the operative knee. The primary outcome is the
presence of an MEB, MOS change or Perm Profile as a result of symptoms related to the operative
knee. This study will demonstrate the attrition rate in active duty soldiers after and ACL
reconstruction and serve to identify predictors via a statistical model to predict who fails active
duty ACL reconstructions.
Progress: This is a retrospective mailed review of functional outcome after ACL reconstruction.
No patients were contacted during FY06; a useable database with current contact information has
not been identified.
443
Detail Summary Sheet
Date: 30 Sep 06 Number: 200065 Status: Completed
Title: Study of the Treatment of Articular Repair (STAR): A Prospective, Longitudinal Within
Patient Evaluation of the Effectiveness (Durability) of Carticel (autologous cultured
chondrocytes) Compared to Non- Carticel Surgical Treatment for Articular Cartilage Defects of
the Knee
Principal Investigator: COL Edward D. Arrington, MC
Department: Surgery/Orthopedic Surgery Facility: MAMC
Associate Investigator(s): MAJ James A. Hall, MC; LTC Doug A. Vermillion, MC; COL (Ret)
Patrick St Pierre, MD
Start - Completion: Funding: Periodic Review:
6/29/2000 - Jun 2006 Genzyme via Henry M. Jackson Foundation 3/21/2006
Study Objective: To compare the effectiveness (durability) of Carticel autologous chondrocyte
implantation in patients who have had an inadequate response to a prior non- Carticel surgical
cartilage repair procedure (including debridement, microfracture, drilling, abrasion arthroplasty or
other surgical treatment) within the previous 3 years for significant articular cartilage defects of
the femoral condyle.
Technical Approach: This study will be a longitudinal, prospective, multicenter, within patient
evaluation of 100 patients with articular cartilage defects of the knee who have had inadequate
response to a prior non-Carticel surgical treatment. Patients who had an inadequate response to a
prior non-Carticel surgical treatment will be implanted with Carticel (autologous cultured
chondrocytes). The overall condition of the knee will be evaluated Using Modified Cincinnati Knee
Rating System at baseline and every 6 months postoperatively. The SF-36 health survey will be
used to assess global health status at baseline and follow-up visits. The primary endpoint of the
study will be time to treatment failure, and will be compared via chart review of consented
patients to the durability of past treatments.
Progress: This protocol closed to patient enrollment in June 2001, with five subjects enrolled at
MAMC. All subjects received study treatment and four completed scheduled follow-up visits. One
subject was reported to the study sponsor and the IRB as lost to follow-up. A study site closure
visit was conducted 18 April 2006. Three internal serious adverse events were reported and
assessed as possible causality with study participation. There were no unreported serious adverse
events at the time of this report.
444
Detail Summary Sheet
Date: 30 Sep 06 Number: 200125 Status: Ongoing
Title: Subacromial Injection of Corticosteroids versus Ketoralac for Treatment of Shoulder
Impingement Syndrome
Principal Investigator: COL Edward D. Arrington, MC
Department: Surgery/Orthopedic Surgery Facility: MAMC
Associate Investigator(s): MAJ Paul M. Ryan, MC; MAJ Bryant G. Marchant, MC; CPT Neil
C. Vining, MC; COL (Ret) Patrick St Pierre, MD; MAJ Christopher J. Wilson, MC; CPT Brian K.
Konowalchuk, MC
Start - Completion: Funding: Periodic Review:
9/5/2000 - Jun 2001 DCI 8/23/2005
Study Objective: To evaluate the difference in pain relief and functional outcome for subacromial
impingement syndrome for patients who are treated with either a subacromial injection of
corticosteroids or a subacromial injection of Ketoralac.
Technical Approach: This double-blind, randomized study will enroll approximately 40 patients
with uncomplicated impingement syndrome for treatment with either subacromial corticosteroids
or Ketoralac. Subjects with subacromial impingement will be given either 6cc 1% lidocaine with
epinephrine and 40 mg Triamcinolone (Control) or 6cc 1% lidocaine with epinephrine and 60mg
injectable Toradol (Test). Patient evaluation will be done at the time of injection and at 4 weeks
post-injection.
Progress: This study closed to patient entry with 48 patients enrolled; 6 during FY06. The
protocol remains ongoing for data analysis. There were no adverse effects that occurred during this
study.
445
Detail Summary Sheet
Date: 30 Sep 06 Number: 205300 Status: Ongoing
Title: Stryker Biotech- OP-1 Bone Morphogenetic Protein, BMP- 7 (HUD)
Principal Investigator: LTC Paul L. Benfanti, MC
Department: Surgery/Orthopedic Surgery Facility: MAMC
Associate Investigator(s): COL Edward D. Arrington, MC; LTC John G. DeVine, MC; COL
Sean D. Ghidella, MC; MAJ James A. Hall, MC; CPT Glenn J. Kerr, MC
Start - Completion: Funding: Periodic Review:
3/8/2005 - Indef Stryker via HDE 2/28/2006
Study Objective: Humanitarian Use Device
Technical Approach: OP-1 Bone Morphogenetic Protein will be used in patients that present
with challenging and difficult to treat injuries that have a very poor success rate using normal
methods and techniques. OP-1 represents the state of the art treatment of injuries that have
challenged surgeons for decades, The success of this product lies in its use of a naturally occurring
substance found in the human body to aid in the initiation of the natural cascade of events that
promote bone healing. The incidence of adverse reactions associated with the implantation is less
than 0.1%.
Progress: An audit was conducted in March 2006 following the report of three patients who
received treatment with OP-1. At that time, the IRB placed oversight of all Humanitarian Use
Devices on the Chief, DCI and DCI Auditor. No adverse effects were reported.
446
Detail Summary Sheet
Date: 30 Sep 06 Number: 205053 Status: Ongoing
Title: A Prospective, Randomized Clinical Investigation of the Cervitech, Inc. Porous Coated
Motion Artificial Disc for Stabilization of the Cervical Spine at One Level between C3-C4 and
C7-T1
Principal Investigator: LTC John G. DeVine, MC
Department: Surgery/Orthopedic Surgery Facility: MAMC
Associate Investigator(s): LTC John I. Iskandar, MC; COL Edward D. Arrington, MC; LTC
Paul L. Benfanti, MC; MAJ Donny M. Melton, MC
Start - Completion: Funding: Periodic Review:
5/31/2005 - Feb 2012 Cervitech via Geneva 2/28/2006
Study Objective: The objective of this clinical study is to evaluate the safety and effectiveness of
the PCM Porous Coated Motion Artificial Disc for treatment of degenerative disc disease compared
to conventional ACDF in patients with DDD and neurological symptoms at one level between C3-
C4 and C7-T1.
Technical Approach: This study plans to enroll 744 patients from areas across the US. Half of
the patients will have surgery to remove the damaged disc and replace it with the study device
(PCM). The other half of the patients will receive the current standard treatment; surgery to
remove the damaged disc and then have the vertebrae fused together. This study will compare
outcomes of disc surgery using the PCM Artificial Disc and the fusion surgery. Prior to surgery
patients will have a physical exam, including x-rays, neurological testing, and either a MRI or CT
scan (unless done in the past 12 months). A bone mineral density scan may be required to
determine bone quality. The patient will also be asked to fill out surveys about neck symptoms,
level of pain, and overall health. Patients will then be assigned to receive either the PCM or fusion
procedure. The patients will not know which treatment they received until after surgery. Patients
will be asked to return to the doctor's office for post-operative follow-up exams at 2-3 weeks, 6
weeks, 3 months, 6 months, 12 months, 24 months, and yearly thereafter until the study is
completed, which may be 7 years after surgery. X-rays and patient surveys will be completed at
these visits.
Progress: This protocol remains open to enrollment with 23 patients enrolled at MAMC; 16
during FY06, all completed the c-spine surgery. One adverse event was reported for a patient with
an extra day hospital stay due to post-op nausea who recovered and is continuing with the study.
Subjects are followed through serial follow- up appointments.
447
Detail Summary Sheet
Date: 30 Sep 06 Number: 206120 Status: Ongoing
Title: A Single Blind, Multi-Center, Randomized, Prospective Clinical Study Comparing
Optecure™ Autograft Extender to Autograft Only in Fusion of the Lumbar Spine
Principal Investigator: ETC John G. DeVine, MC
Department: Surgery/Orthopedic Surgery Facility: MAMC
Associate Investigator(s): COL Edward D. Arrington, MC; LTC Paul L. Benfanti, MC; MAJ
Mark W. Manoso, MC; COL Sean D. Ghidella, MC; MAJ Eric M Bluman, MC
Start - Completion: Funding: Periodic Review:
12/7/2006 - Feb 2009 Exactech, Inc. via The Geneva Foundation N/A
Study Objective: The primary objective of this study is to provide radiographic evidence that
Optecure™ DBM, when used as an autograft extender, produces successful fusion in the lumbar
spine. Secondary objectives include, but are not limited to, evaluating potential differences
between the treatment groups in the occurrence of successful fusion, Oswestry Disability Index
scores, SF-12 scores, and perceived pain as measured by Visual Analog Scales (VAS).
Technical Approach: Consecutive patients, at multiple centers, who are to be treated with
lumbar fusion of 1 or 2 segments (i.e. 2 or 3 consecutive vertebrae) between L2 and Si, will be
screened for participation in this clinical study. Following informed consent, approximately 150
subjects will be enrolled at multiple sites with 75 subjects expected to receive the treatment
material (Optecure™ with autograft) and 75 the control material (autograft). Randomization will
be accomplished at a 1:1 ratio (treatment vs. control). Investigators will remain blinded to the
treatment type until decortication of the primary surgical site is complete. At that time the
Randomization Envelope for the specific subject will be opened and will contain the Randomization
Worksheet denoting the treatment to be used. The subjects will remain blinded to the type of
treatment they receive until their participation in the study is complete (i.e., all follow-up visits
are complete, subject is terminated from the study, or subject withdraws from the study). The
vendor representative will bring the product to the OR for each case. Both the study material
(Optecure) and the control material (autograft) are currently in use at Madigan Army Medical
Center for spinal fusion. Follow-up will continue for 2 years following surgery. Radiographic,
functional, patient health and pain data will be statistically compared between the two groups. A
single, blinded radiologist will analyze fusion success at 6 months, 1 year, and 2 years
postoperatively.
Progress: This greater than minimal risk protocol received initial approval with stipulations
during the convened IRB meeting on 22 August 2006.
448
Detail Summary Sheet
Date: 30 Sep 06 Number: 206081 Status: Ongoing
Title: Magnetic resonance imaging evaluation of adjacent segments after lumbar disc
arthroplasty using the SB Charite implant
Principal Investigator: LTC John G. DeVine, MC
Department: Surgery/Orthopedic Surgery Facility: MAMC
Associate Investigator(s): CPT Ivan J. Antosh, MC; CPT Brian J Woebkenberg, MC; LTC
Stephen M. Yoest, MC
Start - Completion: Funding: Periodic Review:
4/24/2006 - May 2007 DCI N/A
Study Objective: To determine whether or not magnetic resonance imaging is a viable imaging
modality to evaluate adjacent segment after lumbar total disc replacement surgery using the SB
Charite implant.
Technical Approach: Patients consented will have an MRI scan of their spine during a follow-up
clinic visit, which will be evaluated by a radiologist as well as a member of the study staff.
Meaningfulness of the scan will be determined by evaluating the ability to visualize the superior
and inferior endplates as well as the disc space at both the superior and inferior adjacent levels.
Progress: This protocol remains open to patient entry, with three patients enrolled out of five
potential candidates. One patient has completed the post-operative MRI; two patients are waiting
for MRI dates. One potential candidate has been lost to follow-up and could not be contacted;
another patient refused study participation.
449
Detail Summary Sheet
Date: 30 Sep 06 Number: 206082 Status: Ongoing
Title: Magnetic Resonance Imaging Evaluation of Adjacent Segments After Cervical Disc
Arthroplasty Using the PCM Implant
Principal Investigator: ETC John G. DeVine, MC
Department: Surgery/Orthopedic Surgery Facility: MAMC
Associate Investigator(s): CPT Ivan J. Antosh, MC; CPT Brian J Woebkenberg, MC; LTC
Stephen M. Yoest, MC
Start - Completion: Funding: Periodic Review:
4/24/2006 - May 2007 DCI N/A
Study Objective: To determine whether or not magnetic resonance imaging is a viable imaging
modality to evaluate adjacent segment after lumbar total disc replacement surgery using the SB
Charite implant.
Technical Approach: Patients consented will have an MRI scan of their spine during a follow-up
clinic visit, which will be evaluated by a radiologist as well as a member of the study staff.
Meaningfulness of the scan will be determined by evaluating the ability to visualize the superior
and inferior endplates as well as the disc space at both the superior and inferior adjacent levels.
Progress: This protocol is open to patient entry, with five patients enrolled out of eight potential
candidates for the study. Two patients have received their MRIs, three MRIs are pending. Two
candidates were lost to follow-up and could not be contacted. Recruitment of the final patient
continues.
450
Detail Summary Sheet
Date: 30 Sep 06 Number: 205054 Status: Completed
Title: A Phase 2, Double-Blind, Randomized, Placebo-Controlled, Dose-Ranging Study to
Evaluate the Efficacy and Safety of Three Doses of TAK-128 in Subjects with Mild to Moderate
Diabetic Peripheral Neuropathy
Principal Investigator: Vickie R. Driver, DPM
Department: Surgery/Orthopedic Surgery Facility: MAMC
Associate Investigator(s): MAJ Jay C. Erickson, MC; COL Curtis J. Hobbs, MC; COL (Ret)
Charles A. Andersen, MD; Gary P. Degen, DPM; CPT John P. Ney, MC
Start - Completion: Funding: Periodic Review:
5/31/2005 - Mar 2006 Takeda via The Geneva Foundation N/A
Study Objective: Primary objectives of this study are: (1) To determine whether TAK-128 can
significantly improve or slow the rate of progression of diabetic peripheral neuropathy as
measured by nerve conduction velocity. (2) To determine the safety of daily oral doses of TAK-128.
(3) To compare the effects across three doses of TAK-128. Secondary objectives of this study are to
evaluate the effects of TAK-128 on a series of validated clinical measures of neuropathy including:
(1) Quantitative sensory testing (QST), (2) Symptoms and deficits, (3) Quality of Life measures.
The primary variable is the change at 6 months from baseline for composite measure of maximal
nerve conduction velocity. The nerves included in the composite will be the peroneal motor nerve,
median motor nerve, median sensory nerve, and the sural sensory nerve.
The secondary variables are: (1) The change from baseline in vibration perception threshold
measurements. (2) The change in pain scores as assessed by Short-Form McGill Pain
Questionnaire (SF-MPQ). (3) The change in the neurological examination as measured by the
Clinical Neurologic Examination (CNE). (4) The change in the electrophysiologic parameters for
individual nerves, including amplitudes (5) The change in quality of life index as assessed by the
SF-36 Health Survey.
The safety variables include: (1) Adverse events. (2) Clinical laboratory assessments (hematology,
clinical chemistry, urinalysis, HbAlc). (3) ECG results. (4) Vital signs. (5) Physical examinations.
Technical Approach: The study population will comprise approximately 320 male and female
subjects aged 18 to 70, inclusive, considered eligible on the basis of inclusion and exclusion
criteria. Subjects will be randomized in a 1:1:1:1 ratio to 1 of 4 treatment regimens. The total
duration of the study will be approximately 7.25 months and will consist of a Screening Period,
Baseline/Randomization (Day 1), and Treatment Period for up to 6 months, and a follow-up visit 1
week post-treatment. During Screening (Day -21 to Day -1), the eligibility of the subjects will be
assessed. Prior to Randomization, the site staff must confirm that subjects qualify based on the
Inclusion/Exclusion Criteria (see Sections 6.2 and 6.3). Subjects will be randomized to TAK-128 10
mg (two 5 mg tablets QD), TAK-128 50 mg (two 25 mg tablets QD), TAK-128 100 mg (two 50 mg
tablets QD) or placebo. At each visit, subjects will return all unused study medication and have all
required study procedures performed. Study procedures should occur between 6:00 AM and 11:00
AM. Subjects should fast and must not take their daily dose of study medication prior to all visits.
Adverse event (AE) monitoring and concomitant medication use will be reviewed. New study
medication will be dispensed to the subject at all visits except for Weeks 1 and 2 and the Final
Visit (Month 6) or Early Termination Visits.
Progress: This protocol was reported closed at MAMC in November 2005, with no subjects
screened or enrolled.
451
Detail Summary Sheet
Date: 30 Sep 06 Number: 204098
Status: Terminated
Title: Cost of Treating Diabetic Foot Ulcers - At Madigan Army Medical Center
Principal Investigator: Vickie R. Driver, DPM
Department: Surgery/Orthopedic Surgery
Facility: MAMC
Associate Investigator(s): Mary L. Byers, RN
Start - Completion: Funding:
8/26/2004 - Feb 2005 Ethicon, Johnson & Johnson via The Geneva
Foundation
Periodic Review:
7/1/2005
Study Objective: PRIMARY: (1) Determine the yearly institutional cost of treating Diabetic Foot
Ulcers (DFU) at MAMC with advanced and standard care modalities based on a 5-year
retrospective cohort analysis. SECONDARY: (1) Determine rates and predictors of limb
preservation measures. (2) Characterize the effect of 'Advanced Care' (AC) on: "Incidence of
recurrence and infection in existing DFUs," "Incidence amputations," and "Incidence of DFUs." (3)
Identify predictors of amputations. (4) Create a novel detailed database of clinical outcomes,
utilization, and cost in this cohort by incorporating retrospective chart abstraction with the
linkage of existing clinical and billing. (5) Create a Markov Model of disease progression, including
diabetic wound healing, in patients with Diabetes Mellitus (DM). (6) Calculate the cost
effectiveness of advanced care modalities.
Technical Approach: This is a five-year retrospective cohort study of patients with DM who
were seen at Madigan Army Medical Center (MAMC). Patients will be identified in an electronic
claims database using ICD-9 codes for diabetes, diabetic wounds, associated procedures, and
complicating illnesses. Individual claims will then be grouped into cost-driving events using
certain assumptions regarding care based on published literature and investigator knowledge of
current treatment practices in the MAMC system along with data gathered from patient records.
After enrollment into the cohort, all healthcare events will be abstracted directly from the patients'
charts into a relational database which links clinical events to existing claim-based and clinical
databases. Costs will be calculated based upon MAMC institutional cost, as well as Medicare cost
of events. The impact of advanced care modalities on rates of amputation, wound incidence and
recurrence, and infection will be analyzed.
Results will characterize aggregate institutional costs of treatment by site of care (inpatient,
hospital outpatient, pharmacy, home health, etc.) and will also include per-patient and per-disease
event costs. Using existing claims-based methodology for classifying chronic episodes and
measuring co-morbidity, sub-analyses may be performed. Additionally, sub-group analyses will be
conducted on patients who receive certain specified DFU therapies. These results are intended to
describe the institutional costs associated with the care of diabetes and diabetic wounds under
various care modalities. The detailed data this cohort study will provide allows the identification
of individual ulcer events, and can distinguish recurrences from novel ulcers. The effect of
advanced care on the incidence of recurrence, as well as infection, amputation and death can be
calculated as well. The cost-effectiveness of advanced care in terms of amputation-free years, as
well as the number needed to treat (NNT) for advanced care, will be calculated. Costs will be
obtained from the outcomes research department at the MAMC and from published Medicare data.
A Markov Model that characterizes diabetic, and chronic wound states will be used to analyze
effectiveness of various approaches to wound care and disease management. Prediction of long¬
term outcomes, and cost-effectiveness analysis based upon the Markov Model output will be
carried out.
452
Progress: This protocol was officially terminated for cause by the MAMC IRB, 26 September
2006. During the conduct of this retrospective review protocol. Dr. Driver failed to (1) seek HUC
approval for study personnel given access to approximately 550 MAMC subjects' medical records,
(2) maintain the privacy of MAMC subjects' PHI by sending e-mail operative reports to a non-
MAMC employee who was not recognized by the HUC as a member of the study staff, (3) submit
CVs and proof of human subjects training for personnel working on the study, (4) submit data
collection forms for review by the Chairman, IRB, and (5) provide Research Administration Service
with accurate status reports for this protocol prior to leaving her position as Chief, Limb
Preservation Service, Madigan Army Medical Center.
453
Detail Summary Sheet
Date: 30 Sep 06 Number: 205013
Status: Ongoing
Title: A Double-blind, Randomized, Placebo-controlled Phase 2b Study to Establish the Effective
Dose Range and to Evaluate the Safety of Chrysalin in Adult Subjects with a Fractured Distal
Radius
Principal Investigator: COL Sean D. Ghidella, MC
Department: Surgery/Orthopedic Surgery
Facility: MAMC
Associate Investigator(s): OPT Christopher C. Hills, MC;
CPT Sarah D. Beshlian, MC
Start - Completion: Funding:
3/3/2005 - Jan 2008 Orthologic via HMJ
Periodic Review:
10/24/2006
Study Objective: Primary Objective: To determine the time to removal of all rigid immobilization
used to stabilize fracture after single injection of Chrysalin (lug, 3ug, lOug, 30ug) or placebo.
Secondary Objective: To compare clinical assessment of bone healing, inflammation, edema,
motion, and pain at fracture site, as well as to compare radiographic evaluation with global
assessment of bone healing. Safety data will be collected on incidence and severity of emergent
adverse events and laboratory assessments.
Technical Approach: This trial is a double-blind, randomized, placebo-controlled study to
establish the effective dose range of a single percutaneous injection of Chrysalin (lug, 3ug, lOug or
30ug) in subjects being treated with surgical reduction of a distal radial fracture. At MAMC, the
study will be conducted by the Orthopedic Service. 15-20 MAMC subjects may be enrolled for a
total of 500 subjects to be enrolled in the study overall. Subjects will be consented and screened in
the orthopedic service in collaboration with the research nurse. Subjects will then be scheduled for
surgical reduction on a weekday, within a schedule that allows time for pre-study assessments to
be done. Study assessments will include physical examination and history, baseline radiographs,
pain questionnaire, CBC, serum chemistry, EKG, and serum HCG as appropriate, prior to study
treatment. Chrysalin or placebo will be administered under fluoroscopic guidance in the OR as a
single percutaneous injection, after surgical reduction of the fracture. Objective response to
treatment will be measured with serial radiographs, grip strength and rage of motion. Ongoing
efficacy and safety evaluations will include, subject-rated pain scales and laboratory tests. Subjects
will be followed by the Orthopedic Service for 52 weeks, including a referral to hand therapy for a
minimum of 4 weekly sessions.
The primary analysis will be performed including all subjects who received their study injection
and have had at least 8 weeks of follow-up. A secondary analysis will use a modified intent-to-treat
sample including all subjects who have received study drug, regardless of follow-up. Safety
analyses will include all enrolled subjects. Subjects who become pregnant will be followed to
determine the outcome of the pregnancy.
Progress: This protocol closed to enrollment with four subjects enrolled; three completed all study
visits, and one remains in follow-up until February 2007. Three adverse events were reported but
assessed as unrelated to study participation.
454
Detail Summary Sheet
Date: 30 Sep 06 Number: 206009 Status: Ongoing
Title: A Randomized Study of Volar Fixed- Angle Plate Fixation Versus Closed Management for
Fractures of the Distal Radius
Principal Investigator: COL Sean D. Ghidella, MC
Department: Surgery/Orthopedic Surgery Facility: MAMC
Associate Investigator(s): LTC John G. DeVine, MC; COL Edward D. Arrington, MC;
Elizabeth E. Miklos-Essenberg, PT; CPT Aaron H. Hoblet, MC; CPT Joshua P. Herzog, MC
Start - Completion: Funding: Periodic Review:
4/19/2006 - Apr 2007 via Geneva 9/29/2006
Study Objective: To determine the effectiveness of a volar fixed angle plate in distal radius
fractures.
Technical Approach: The study will enroll 20 patients in each arm for a total of 40 patients.
Subjects will have to meet the following inclusion criteria: 18-99 year old, Distal Radius Fracture,
Active Lifestyle, Able to tolerate an operation., Articular Step-off <2mm, Articular Diastasis of
<2mm, < 20 deg of dorsal angulation and dorsal comminution of >1/3 of the AP diameter of the
radial shaft. Subjects will be excluded for volar oblique fracture (Volar Bartons), die punch
fractures, associated DRUJ injury, and associated trauma (polytrauma). Subjects will be evaluated
via the following outcomes: at time zero, 6 Weeks, 3 Months (M), 6 M, 12 M, 18 M and 24 M:
Grip/Pinch strength, ROM, SF-36, Patient-rated wrist evaluation questionnaire (PRWE), DASH,
Missed work days, Time (days) till Radiographic Union, and Complications.
Progress: Funding for this protocol has become available. Enrollment remains pending receipt of
a CRAD A/SOW from The Geneva Foundation and the CRAD A/SOW approval process through
MAMC DCI, CJA and CIRO.
455
Detail Summary Sheet
Date: 30 Sep 06 Number: 205079
Status: Ongoing
Title: Microsurgery Training Utilizing The Rat (rattus norvegieus)
Principal Investigator: COL Sean D. Ghidella, MC
as a Teaching Model
Department: Surgery/Orthopedic Surgery
Facility: MAMC
Associate Investigator(s): LTC John G. DeVine, MC; LTC Paul L. Benfanti, MC; MAJ Karen
C. Baker, MC; COL Edward D. Arrington, MC
Start - Completion: Funding:
7/13/2005 - May 2008 DCI
Periodic Review:
7/30/2006
Study Objective: The establishment of a microsurgical laboratory utilizing appropriate
inanimate materials and anesthetized rats for the teaching and practice of microsurgical
techniques will significantly enhance the skills of MAMC surgical staff and residents. It will also
correct a deficiency in the Orthopedic Surgery Residency Program (lack of formal micro surgical
training) identified by the Residency Review Committee for Orthopedics. Availability of such a
laboratory for skill maintenance and enhancement is the standard at teaching institutions that
perform microsurgery.
Technical Approach: BASIC MICROSURGICAL TECHNIQUES COURSE: This course will
consist of five days of progressive microsurgical techniques utilizing didactic or videotape
instruction, inanimate "dry labs" for basic instrumentation/orientation training, and practice of
prescribed microsurgical procedures utilizing live rats under general anesthesia. The general
course flow and animal utilization will be as follows: Day 1: 1) Orientation, course objectives; 2)
Basic principles/applications of microsurgery -care and use of surgical microscopes and
instruments; 3) Microsurgical instrument lab; 4) Microsuture handling/knot tying/tissue handling;
5) suturing/tissue/handling/"arteriotomy" repair lab with inanimate training materials. Day 2: 1)
Rat care and use in microsurgery training; 2) Principles/techniques for end-to-end (ETE) arterial
anastomosis; 3) ETE anastomosis-basic technique lab using inanimate training materials; 4) ETE
arterial anastomosis lab using live, anesthetized rat. Day 3: 1) Principles/techniques for ETE
venous anastomosis. 2) ETE venous anastomosis lab with live, anethestized rat; 3)
Principles/techniques for end-toside (ETS) arterial anatomosis; 4) ETS arterial anastomosis lab
with live, anethestized rats. Day 4: 1) Principles/techniques for interpositional venous graft; 2)
Interpositional venous graft lab with live, anesthetized rats; 3) Principles/techniques for
neurorrhaphy; 4) neurorrhaphy lab with live, anethestized rats. Day 5: 1) Specialty- specific
instruction/laboratory with live, anethestized rats; 2) Vasovasostomy. 3) Fallopian tube
anastomosis; 4) Micro-tendon repair; 5) Free vascular tissue transfer; 6) Course
Summary/Review/ Critique .
UROGENITAL (OB/GYN, UROLOGY) MICROSURGERY TRAINING: This course will consist of
two (2) consecutive, eight (8) hour days of training in the instrumentation, principles and
performance of common urogenital microsurgery techniques and procedures. Course content will
generally, but not necessarily follow the detailed synopsis below. Day 1: Introduction to
microsurgery (video, slides, written materials, discussion). Day 2: Principles of urogenital surgical
site assessment and repair (video, slides, written materials, discussion).
ADVANCED MICROSURGERY TECHNIQUES (AMT) COURSE: Advanced microsurgery courses
will consist of five (5) consecutive, eight (8) hour training days. Participants in advanced
microsurgery training course will plan their proposed advanced procedures with the course
instructor(s) prior to course commencement. Course instructors will confer with the DCI
Veterinarian regarding proposed advanced procedures and animal species preferences at least 30
days prior to course commencement, in order to ensure adequate consideration for animal
456
availability, care and postoperative well being. Advanced procedures may consist of techniques
such as limb/digit replantation, free vascularizated soft tissue or bone grafts, advance neurologic
or urogenital reconstructions, anatomical augmentation, organ transplantation, etc. NOTE:
Because of the variety of subspeciality- specific procedures to be considered for AMT training, it is
not feasible to list or describe specific procedures in this protocol. AMT course schedules and
proposed procedures will require MAMC IACUC approval PRIOR to course commencement.
Training coordinators for AMT courses will provide reasonable description of the proposed
procedures, in writing and will discuss potential procedure-specific post-operative complications
for consideration during IACUC review of proposed AMT course schedules.
Day 1: Introduction to microsurgery (video, slides, written materials, discussion) Instrumentation
and instrument handling, suture and supplies, suture manipulation and knot tying (video, slides,
written materials, discussion) Proper use of the surgical microscope and surgical loupes, suture
manipulation and knot tying (laboratory exercise; inanimate training materials) Procedures for
end-to-end (ETE), end-to-side (ETS), and side-to-side (STS) anastomosis of tubular organs, and
longitudinal defect repair (video, slides, written materials, discussion- Practice ETE, ETS, and
STS tubular anastomoses, and longitudinal defect repair (laboratory exercise; inanimate training
materials or rat cadaver). Day 2: Principles of urogenital surgical site assessment and repair
(video, slides, written materials, discussion) Preparation and suturing techniques for fallopian
tube or vas deferens repair/reconstruction (video, slides, written materials, discussion. Practice
fallopian tube or vas deferens repair/reconstruction techniques using rat uterus and femoral
artery/vein, with surgical loupes and microscope (laboratory exercise; anesthetized rat) Elective
instrumentation/procedures laboratory session (e.g. continuation of tubal/vas deferens
reconstruction/repair techniques; ureteral injury repair techniques; basic microvascular,
microneural, microlymphatic repair techniques; urogenital applications of the non-penetrating
Vascular Closure System- VCS, US Surgical Inc. etc) (laboratory exercise; inanimate tissue or
anesthetized rat)
ADVANCED MICROSURGERY TECHNIQUES (AMT) COURSE:
Advanced microsurgery courses will consist of five (5) consecutive, eight (8) hour training days.
Participants in advanced microsurgery training course will plan their proposed advanced
procedures with the course instructor(s) prior to course commencement. Course instructors will
confer with the CIF veterinarian regarding proposed advanced procedures and animal species
preferences at least 30 days prior to course commencement, in order to ensure adequate
consideration for animal availability, care, and postoperative well being, /advanced procedures
may consist of techniques such as limb/digit replantation, free vascularized soft tissue or bone
grafts, advance neurologic or urogenital reconstructions, anatomical augmentation, organ
transplantation, etc. Note: Because of the variety of sub-specialty specific procedures to be
considered for AMT training, it is not feasible to list or describe specific procedures in this protocol.
AMT course schedules and proposed procedures will require 60 MDG IACUC approval PRIOR to
course commencement. Training coordinators for AMT courses will provide reasonable description
of the proposed procedures, in writing, and will discuss potential procedure-specific postoperative
complications for consideration during IACUC review of proposed AMT course schedules. Day 1:
Review of microsurgery principles and techniques (video, slides, written materials, discussion.
Presentations/discussion of first proposed advanced procedures, including postoperative
management/monitoring issues, etc. (video, slides, written materials, discussion. Practice first
advance procedures-terminal /non-survival; instructor evaluation of participant technical
proficiencies (laboratory exercise; anesthetized rat, rabbit, pig, sheep/goat terminal/non-survival.
Day 2: Perform advance procedures described on Day 1, morning and practiced Day 1, afternoon;
recovery of anesthetized animal (laboratory exercise; anesthetized rat, rabbit, pig, sheep/goat.
Postoperative assessment of morning surgery animal/operative site; presentations/discussion of
second proposed advanced procedures, including postoperative management/monitoring issues,
etc. (video, slides, written materials, discussion. Day 3: Assessment of Day 2 animal/operative site;
457
perform advanced procedures described Day 2 afternoon on new animal; recovery of anesthetized
animal (laboratory exercise; anesthetized rat, rabbit, pig, sheep/goat. Presentations/discussions of
third proposed advance procedure, including postoperative management/monitoring issues, etc.;
Postoperative assessment of morning surgery animal/operative site, and Day 2 animal /operative
site (video, slides, written materials, discussion); Day 4: Assessment of Day 2 & 3
animals/operative sites; perform advanced procedures; Presentations/discussion of fourth proposed
advanced procedures, including postoperative management/monitoring issues, etc.; postoperative
assessment of Day 3 animal/operative site (video, slides, written materials, discussion); Day 5:
Assessment of Day 3 animal/operative site; perform advanced procedures animal- terminal/non¬
survival procedure (laboratory exercise; anesthetized rat, rabbit, pig, sheep/goat, terminal/non¬
survival).
Progress: One training lab was held, using two rats for microsurgery training. Four urology
residents were trained during the lab.
458
Detail Summary Sheet
Date: 30 Sep 06 Number: 201112 Status: Completed
Title: Post-operative Shoulder Pain: A Prospective Randomized Trial Comparing the Pain
Infusion Pump to the Pre-induction Interscalene Block
Principal Investigator: CPT Joshua P. Herzog, MC
Department: Surgery/Orthopedic Surgery Facility: MAMC
Associate Investigator(s): COL Edward D. Arrington, MC; MAJ Daniel W. White, MC
Start - Completion: Funding: Periodic Review:
9/14/2001 - Feb 2002 DCI 6/27/2006
Study Objective: Determine the efficacy of the pain control infusion pump (PCIP) in controlling
post-operative pain in patients undergoing shoulder surgery.
Technical Approach: This study will enroll 50 consecutive patients scheduled for elective
shoulder surgery to address subacromial impingement syndrome with or without a rotator cuff
tear; or, acromio-clavicular degenerative disease. Randomization of consented patients to Group A
(pain control infusion pump) or Group B (pre-induction interscalene block) will be determined
during the preoperative evaluation. Group A patients will undergo surgery and then have the
catheter placed in the subacromial space and attached to the "On'Q Pain Management System"
with a standardized dose of 0.5% Marcaine. Group B patients will undergo a standardized pre¬
induction interscalene block utilizing the current standard technique by the anesthesia provider
with 0.5% Marcaine. All patients will receive standardized anesthesia and post-operative standard
of care, including a PCA for IV narcotic use overnight. The amount of narcotic use, pain
medications, nauseas medications and difficulties will be recorded. A questionnaire will be
completed the day after surgery and will consist of a 10-centimeter visual analog scale for pain,
nausea, and pain control satisfaction as well as narcotic and non-narcotic analgesic use tabulation.
Patients will follow-up at 72 to 96 hours for operative site evaluation. The total use of all narcotic
and non-narcotic pain meds will be recorded from the time of discharge to this appointment. Group
A patients will have the pain control infusion pump catheter removed, the number of narcotic and
non-narcotic pain meds used totaled and the same questionnaire used previously completed.
Patients will keep a running total of all narcotic and non-narcotic pain meds used from the time of
this appointment until the follow-up 7 to 8 days after surgery. At that time the same questionnaire
will be administered. Any complications will be continuously followed and data collected until the
condition has been resolved, stabilizes, or the study is concluded.
A power analysis will be completed after 10 patients have completed the three questionnaires.
Data analyzed: comparison of visual analog scores for pain, nausea, and overall pain control
satisfaction. Direct comparison: amount of narcotic and non-narcotic pain medications used. Based
on the statistical analysis and the power analysis, the study population size will be determined
based on the number of patients that will be required to achieve statistically significant results.
The study will then be continued until the appropriate number of patients has been enrolled.
Progress: This protocol was reported as completed during FY06, with fifty subjects enrolled. An
interim analysis was conducted with 44 data sets; 23 pain control infusion pump and 21
interscalene block. Although results showed increased nausea for the pain controlled infusion
pump on post-operative day 3, both pain control mechanism seem to have equal efficacy. It was
determined though a new power analysis that 1,200 subjects would be needed to determine
statistical significance. This protocol was presented at the Western Orthopaedic Annual Meeting.
459
Detail Summary Sheet
Date: 30 Sep 06 Number: 202091 Status: Terminated
Title: A Prospective, Randomized, Stratified, Parallel Group, Comparison Study of the Healing
Rate of Chronic Neuropathic Ulcers Treated with Hyalofill versus Regranex
Principal Investigator: Monica H. Schweinberger, DPM
Department: Surgery/Orthopedic Surgery Facility: MAMC
Associate Investigator(s): COL (Ret) Charles A. Andersen, MD; Gary P. Degen, DPM; Vickie
R. Driver, DPM
Start - Completion: Funding: Periodic Review:
10/8/2002 - Jun 2003 Convatec via The Geneva Foundation 6/28/2005
Study Objective: Compare the treatment time required for complete wound repair of two wound
healing products currently available for diabetic would care (Hyalofill VS Regranex).
Technical Approach: This is a prospective, randomized, stratified, comparative, parallel group,
one center clinic trial, comparing the time to wound closure of indolent ulcers healed by Hyalofill
protocol of wound care to protocol of Regranex gel. MAMC will enroll 55 total patients. Patient will
be stratified according to ulcer location to randomization and will be assigned to either Regranex
or Hyalofill protocol. All subjects will participate in the 20 week study or to complete 100% re-
epithelization, whichever occurs first. Time to wound closure will be measured in weekly
increments.
Progress: This protocol was terminated by Dr. Schweinberger in July 2006. The original PI, Dr.
Driver, left MAMC employment in November 2005, and the staff of Limb Preservation Service had
no interest in pursuing this topic. There are no analyses or study results to present. A total of 20
patients enrolled in this study at MAMC; 14 received study treatment, 3 were screen failures and
3 were removed by the previous PI.
460
Detail Summary Sheets
Otolaryngology Service, Department of
Surgery
461
Detail Summary Sheet
Date: 30 Sep 06 Number: 204009
Status: Completed
Title: Evaluation of Dizziness / Vertigo by MRI/MRA: A Clinical Outcomes Study
Principal Investigator: MAJ Brian J. Baumgartner, MC
Department: Surgery/Otolaryngology
Facility: MAMC
Associate Investigator(s): None.
Start - Completion: Funding:
10/31/2003 - Mar 2004 DCI
Periodic Review:
10/15/2004
Study Objective: To ascertain the clinical usefulness of obtaining magnetic resonance imaging or
magnetic resonance angiography studies of the posterior fossa for the patient with isolated
dizziness or vertigo.
Technical Approach: Retrospective chart review of all patients over the age of 18 who have had
a MRI and/or MRA of the posterior fossa with the words dizziness and/or vertigo in the reason for
request field will be performed. The MRI/MRA results will be reviewed. Their charts will then be
identified and reviewed to ascertain the indications for the study. The records will be reviewed for
the diagnosis and for management decisions based on the MRI/MRA to ascertain the clinical
usefulness of this study for the above indications.
Progress: Research Administration Service requested that the HUC approve a change of status
for this protocol from ongoing to completed, as a final report was submitted last year and the PI
has been non-responsive to requests for information via Outlook. HUC approved closure of this
protocol in November 2005.
462
Detail Summary Sheet
Date: 30 Sep 06 Number: 205052
Status: Ongoing
Title: MET™ Fully Implantable Ossicular Stimulator Clinical Trial Protocol
Principal Investigator: MAJ James V. Crawford, MC
Department: Surgery/Otolaryngology
Facility: MAMC
Associate Investigator(s): LTC Carlos R. Esquivel, MC; LTC Dale A. Ostler, MS
Start - Completion: Funding:
5/31/2005 - May 2008 DCI via Otologics, LLC
Periodic Review:
8/14/2006
Study Objective: To determine the safety and effectiveness of a Fully Implantable hearing
device.
Technical Approach: The Fully- Implantable MET Ossicular Stimulator is an implanted
prosthetic device, which bypasses the external auditory canal and mechanically stimulates the
ossicles directly to take advantage of the patient's residual hearing. This system is intended to
provide amplification with adequate gain, output and superior sound quality to that achieved with
conventional, acoustic hearing aids. The target population includes patients who also want the
convenience, and features of a fully implantable device which will provide them with amplification
in situations where acoustic hearing aids were prohibited such as showering, swimming, sleeping,
and various recreational activities.
A Phase I and II multi-site, clinical trial will be conducted with up to 90 patients at 15
investigational sites. The safety endpoints of air and bone conduction are assessed at 3, 6 and 12
month post implantation test intervals to demonstrate that residual hearing is not clinically,
significantly affected by the implantation of the fully implantable device. The efficacy endpoints at
each test interval are to demonstrate that the fully implantable hearing system is equal to or
better than an appropriately fit air conduction hearing aid. The particular areas of comparison are
for audibility of soft sounds, speech understanding in quiet and in noise, and perceived benefit by
the patient as determined by a questionnaire. The approach to design and analysis has features of
single-subject studies, reflecting repeated-measures, within- subjects design, wherein each subject
acts as his/her own control.
Progress: This protocol was not initiated at MAMC during FY06; however, the company
producing the implants received FDA approval and enrollment can proceed.
463
Detail Summary Sheet
Date: 30 Sep 06 Number: 204042 Status: Terminated
Title: Rapid Employment of Acetylcysteine Treatment for Otologic Recovery (REACTOR), A
Prospective, Multicenter, Randomized, Double-blind, Parallel, Placebo-controlled Study
Assessing the Efficacy of the Nutritional Supplement N- Acetylcysteine Treatment of Acute
Acoustic Trauma
Principal Investigator: MAJ James V. Crawford, MC
Department: Surgery/Otolaryngology Facility: MAMC
Associate Investigator(s): LTC Douglas M. Sorensen, MC; Allyson A. Peterson, RN; Paul B.
Asetre, RN; LTC John J. Simmer, MC; CPT Dan F. Ohama, MS; Vincent D. Eusterman, MD;
MAJ Marjorie A. M. Grantham, MS; LTC Dale A. Ostler, MS; LTC Carlos R. Esquivel, MC
Start - Completion: Funding: Periodic Review:
4/20/2004 - Jun 2005 Dept, of the Navy (BUMED) via MIPR 4/10/2006
Study Objective: To determine if the administration of oral N- Acetylcysteine within the four
hours following acute acoustic trauma, sustained by soldiers in the course of military training, can
reduce permanent hearing loss, reduce tinnitus severity, and increase the speed of recovery from
temporary hearing loss.
Technical Approach: This is a prospective, multicenter, randomized, double-blind, parallel,
placebo-controlled study assessing the efficacy of the nutritional supplement N- Acetylcysteine
treatment of acute acoustic trauma in approximately 190 male and female soldiers across four
sites. Subjects will be recruited during routine weapons training following self-reported hearing
loss symptoms. Each potential subject will undergo screening audiogram and based on the results
be returned to training or referred for additional evaluation. Eligible subjects will be asked to
complete a tinnitus questionnaire, a demographics and noise exposure history questionnaire, and
then be randomized to either N- Acetylcysteine (NAC) or placebo. Each subject will continue on
study medication for seven days and return for audiometric testing and follow-up questionnaires
on Days 2 through 4 and again on Day 7, Day 30, and Day 90.
Outcome measures include: (1) mean absolute hearing threshold at each frequency in each ear at
each follow-up interval, (2) mean change from baseline (threshold shift) at each frequency in the
same ear, at each follow-up interval, (3) mean change from baseline (threshold shift) in the
average frequencies of 2,3,4K HZ (most sensitive to noise trauma) in each ear at each follow-up
interval and at 30 days, (4) mean improvement (change from worst level) at each frequency in the
same ear at 30 days, (5) rate of recovery from worst hearing level at each frequency and at the
2,3,4 kHz average over the study period, (6) mean tinnitus loudness score (0-10) at each follow-up
interval compared between treatment groups, (7) frequency of report of subjective hearing
difficulty (yes/no) compared between treatment groups, and (8) following independent variables
compared between treatment groups: (a) noise exposure characteristics, (b) age, (c) race and
ethnicity distribution, (d) baseline hearing thresholds, (e) hearing thresholds at the time of initial
evaluation, (f) reported use of medications, and g) smoking history compared between treatment
groups.
Progress: This protocol has been terminated due to difficulty enrolling subjects at all sites of this
multi-center study. Over 40 subjects were screened to date, but none met enrollment criteria.
464
Detail Summary Sheet
Date: 30 Sep 06 Number: 206058 Status: Completed
Title: Effect of Smoking on Rate of Post-tonsillectomy Hemorrhage
Principal Investigator: CPT Sean M. Demars, MC
Department: Surgery/Otolaryngology Facility: MAMC
Associate Investigator(s): MAJ James V. Crawford, MC; CPT Wayne J. Harsha, MC
Start - Completion: Funding: Periodic Review:
1/31/2006 - Feb 2006 DCI N/A
Study Objective: To determine the effect of smoking on the incidence of post-tonsillectomy
hemorrhage in adults at MAMC over the last five years
Technical Approach: A search of ORMA will be performed to identify all patients treated by the
otolaryngology service from June 2000 to September 2005. This subset of patients will then be
further divided to isolate those older than 18 who underwent a tonsillectomy as either the primary
or secondary procedure for any diagnosis. Special note will be made of any patients with the
preoperative diagnosis of post-tonsillectomy bleed or control of post-tonsillectomy hemorrhage. The
billing department will also be contacted to identify all patients with the CPT codes of 42826 and
42821 corresponding to tonsillectomy and adenotonsillectomy greater than 12 years of age
respectively. Patients with CPT codes for varying severities of oropharyngeal hemorrhage control
(42960-62) will also be collected. These two subsets of patient will be combined and any repetitions
will be removed. Also to be removed are all patients younger than 18 and patients undergoing
tonsillectomy for oropharyngeal or head and neck cancer. The records of the remaining patients
will be evaluated to determine if the patients admitted to currently smoking in either the initial
preoperative exam in the otolaryngology clinic, or in the preoperative examination performed by
anesthesia. The records would further be searched to determine which patients sought medical
attention within 15 days of their surgery and why. The rate of post-tonsillectomy hemorrhage in
smokers vs. non-smokers would then be compared using the chi-squared test to determine
statistical significance.
Progress: This protocol was reported as completed during FY06, with 1,014 chart reviews
conducted. A poster was presented at AAO-HNS meeting in September, submission for publication
is pending.
465
Detail Summary Sheet
Date: 30 Sep 06 Number: 206044 Status: Completed
Title: Review of Postoperative Complications after BAHA Implantation at Madigan AMC and
Virginia Mason MC
Principal Investigator: CPT Sean M. Demars, MC
Department: Surgery/Otolaryngology Facility: MAMC
Associate Investigator(s): LTC Carlos R. Esquivel, MC; Douglas D. Backous, MD
Start - Completion: Funding: Periodic Review:
1/9/2006 - Jan 2007 DCI N/A
Study Objective: To determine the rate and type of postoperative complications from bone
anchored hearing aid placement (BAHA) at MAMC and VMMC.
Technical Approach: This study is a retrospective chart review including all patients that have
had BAHA placement at either Madigan AMC or Virginia Mason MC in the last five years;
focusing on the number and type of complications associated with BAHA placement. Rates of
various complications will be reported along with any need for additional procedures or course of
antibiotics, any failure of osseointegration or loss of implant, and any skin reactions around the
implant.
Progress: This protocol was reported completed during FY06, with 81 patients included in the
chart review. A poster presentation is pending at the Western Sectional meeting of the Triological
Society in February 2007. Submission for publication is also pending.
466
Detail Summary Sheet
Date: 30 Sep 06 Number: 205050 Status: Ongoing
Title: Celecoxib Versus Oxycodone in Uvulopalatopharyngoplasty Surgery: A Comparison of
Post-Operative Risks and Benefits
Principal Investigator: CPT Matthew R. Grafenberg, MC
Department: Surgery/Otolaryngology Facility: MAMC
Associate Investigator(s): Vincent D. Eusterman, MD; CPT Roy F. Thomas, MC
Start - Completion: Funding: Periodic Review:
9/28/2005 - Oct 2006 DCI 5/26/2006
Study Objective: To determine if the drug valdecoxib (Bextra) is associated with less pain,
nausea, bleeding and total cost as compared to oxycodone when used in the immediate pre- and
post-operative period with uvulopalatopharyngoplasty (UPPP) surgery.
Technical Approach: All patients 18 years or older who are diagnosed as having heroic snoring
or obstructive sleep apnea syndrome (OSAS) and deemed appropriate surgical candidates based on
history and physical exam are eligible for inclusion in this study. There will be approximately 75
patients randomly assigned to three different study groups, (2 experimental and one control).
These groups include (1) patients receiving a single pre-operative dose of Bextra and post¬
operative placebo, (2) patients receiving a pre-operative dose of placebo and post-operative Bextra
(20 mg x 5d) and (3) patients receiving both pre-operative and post-operative placebo. Patients will
be contacted 14 days after surgery with telephone calls to ensure completion of pain/nausea logs. A
post-operative visit at 4 weeks will be scheduled.
The primary outcome variables will be duration/total amount of narcotic usage (oxycodone) and
pain scores. Secondary outcome variables will include post-operative nausea and vomiting,
bleeding and cost analysis. The number of days and total amount of narcotic usage will be
calculated for each of the three study groups. Pain and nausea/vomiting will be measured by visual
analog scales (VAS). Bleeding rates will be calculated based on those patients requiring
intervention to stop bleeding either in the emergency room (ER) or the operating room (OR) by an
ENT physician. Cost will be calculated based on price of medications used for each study group,
additional unscheduled clinic visits and any ER/OR interventions performed.
Progress: This protocol remains open to patient entry at MAMC; however enrollment has not yet
been initiated due to deployments of study staff.
467
Detail Summary Sheet
Date: 30 Sep 06 Number: 205120
Status: Ongoing
Title: Complications and Audiologic/Tympanometric Findings in
and Cleft Palate
Children with Cleft Lip/Palate
Principal Investigator: CPT Matthew R. Grafenberg, MC
Department: Surgery/Otolaryngology
Facility: MAMC
Associate Investigator(s): LTC Carlos R. Esquivel, MC
Start - Completion: Funding:
8/18/2005 - Sep 2005 DCI
Periodic Review:
8/10/2006
Study Objective: To determine if the surgical procedure of myringotomy with tympanostomy
tube placement is associated with an increased risk of complications as compared with no surgical
intervention in the cleft lip/palate and cleft palate population.
Technical Approach: This is a retrospective chart review of 88 patients, 18 years of age and
younger, diagnosed with cleft lip/palate or cleft palate treated at MAMC over a 15-year period.
Children with craniofacial anomalies without cleft/palate or cleft palate and those children with
isolated cleft lip or cleft lip and alveolus will be excluded from the study. Patients will be divided
into multiple groups based on type of cleft and whether surgical intervention with myringotomy
and ventilation tube placement was performed. Comparisons will be made between groups with
respect to complication types and rates, audiologic findings, tympanometric findings and
functionality of tube as described above in the dependent variables section. The primary outcome
variables will be complication rates, audiologic and tympanometric results. Other outcome
variables will include the effect of cleft type on the need for at least one surgical procedure, effect
of cleft type on the total number of surgical procedures, effect of cleft type on average age of 1st
surgical procedure and average duration of functional tube based on both type of cleft and tube.
Data Analysis: Complication rates will be analyzed and compared on several different fronts.
Patients will be divided into those that underwent surgical intervention and those that did not to
determine if an association exists between surgical intervention and complication rate. In the
group of patients where complications were noted to occur, the average number of ventilation
tubes per patient will be calculated and compared to the group of patients that had ventilation
tubes placed but no complications to determine if there is an association between increased
number of procedures and complication rates. In addition, complication rates will be calculated for
each type of tube and a comparison made between groups. Types of complications will also be
calculated for each variety of tube and a comparison made between groups. Audiologic results will
be reported as pure tone averages (PTA) as previously described. Overall PTA will be calculated
for both patients undergoing surgical intervention and those that did not to determine if an
association exists between hearing status and tube placement. In addition, both groups of patients
will be further broken down according to cleft type to determine if this factor has any effect on
hearing status. Those patients undergoing myringotomy with ventilation tube placement will be
broken down into pre- and post-operative PTA values to determine if surgical intervention had an
immediate short-term effect on hearing. In addition, long-term PTA at approximately 1 and 5
years after initial myringotomy with ventilation tube placement will be calculated for the surgical
group (as previously described) and comparisons made to both the original pre-operative and non-
surgical group PTA values to determine if surgical intervention has a long-term effect on hearing.
Tympanometric results will be classified as normal or abnormal based on criteria previously
described. Patients will once again be divided into two groups based whether they underwent
surgical intervention. Comparisons between the two groups will be made to determine if an
association exists between abnormal tympanograms and surgical intervention. In addition, each
group will be further broken down by cleft type to determine if this variable had any effect on
468
tympanogram results. Other outcome measures to be analyzed include the effect of cleft type on
the need for at least one surgical procedure, effect of cleft type on the total number of surgical
procedures, effect of cleft type on average age of the 1st surgical procedure and the average
duration of functional ventilation tube based both on type of cleft and tube.
Progress: This retrospective review protocol has completed data collection from 88 subject charts.
Statistical analysis is being conducted. No further chart reviews will be required.
469
Detail Summary Sheet
Date: 30 Sep 06 Number: 206125
Status: Ongoing
Title: Base of Tongue Reduction for Persistent Obstructive Sleep Apnea Using the Coblator II
System: A Pilot Study
Principal Investigator: CPT James M. Poss, MC
Department: Surgery/Otolaryngology
Facility: MAMC
Associate Investigator(s): CPT Samuel A. Spear, MC, USAF;
MAJ Mark A. Criswell, MC
Start - Completion: Funding:
11/17/2006 - Jun 2007 DCI
Periodic Review:
N/A
Study Objective: To evaluate the efficacy of coblator reduction of base of tongue in patients who
have persistent obstructive sleep apnea (OSA) after prior palate surgery.
Technical Approach: Reduction of Base of Tongue with Coblator II plasma wand with integrated
cable (8000 J delivered over 2 minutes). Three separate lesions will be made at each of three sites
(midline and paramedian bilaterally). Three procedures will take place separated by a time period
of at least 1 month.
Progress: This greater than minimal risk protocol received initial approval with stipulations
during the convened IRB meeting on 26 September 2006.
470
Detail Summary Sheet
Date: 30 Sep 06 Number: 206020
Status: Ongoing
Title: Clinical Survey of Community Physicians: Post-Tympanostomy Tube Placement and
Swimming Precautions/Treatment Otitis Media with Effusion
Principal Investigator: CPT James M. Poss, MC
Department: Surgery/Otolaryngology
Facility: MAMC
Associate Investigator(s): MAJ James V. Crawford, MC
Start - Completion: Funding:
11/30/2005 - Dec 2006 DCI
Periodic Review:
N/A
Study Objective: Objective: to determine the differences regarding Post-tympanostomy
Swimming Precautions and treatment of Otitis Media with Effusion between Otolaryngologists,
Pediatricians, and Family Practice physicians.
Technical Approach: Anonymous information will be placed into a database whereby simple
statistical analyses can be performed (averages, means, Chi-squared) to look for statistical
significance.
Progress: Questionnaires were forwarded to 1,116 otolaryngologists, pediatricians and family
practitioners in the Pacific Northwest. Over 200 practitioners responded to the questionnaires.
The data was presented in poster format at AAO-HNS annual meeting in September 2006. The
protocol remains ongoing to complete final paper for submission to a peer reviewed journal.
Conclusions: Recommendations for swimming precautions are not universal between the medical
specialities that routinely see patients with tympanostomy tubes. Most primary care physicians
and many otolaryngologists continue to prescribe water precautions to patients with tubes in
place, despite published articles that have shown no reduction in the incidence of otorrhea from
barrier devices or avoidance of swimming.
471
Detail Summary Sheet
Date: 30 Sep 06 Number: 203016 Status: Expired
Title: Pediatric Bronchoesophagology Laboratory Using Swine (Sus scrofa)
Principal Investigator: LTC Douglas M. Sorensen, MC
Department: Surgery/Otolaryngology Facility: MAMC
Associate Investigator(s): Andrew Inglis, M.D.; MAJ Andrew B. Silva, MC
Start - Completion: Funding: Periodic Review:
10/9/2002 - Oct 2005 DCI 9/14/2005
Study Objective: To familiarize the junior otolaryngology residents at MAMC and the UW and
the Pediatric Surgery fellows at CHMC, with the endoscopic instrumentation and techniques
required to evaluate and treat the tracheobronchial tree and esophagus in children. This would
include familiarization with esophageal and tracheal foreign body removal, rigid and flexible
endoscopic techniques and endobronchial laser use. Familiarity with these techniques would allow
an increased margin of safety for children undergoing these procedures and better prepare the
endoscopist to assist and then perform these procedures when necessary. Increased endoscopic
training experiences will increase operative efficiency and minimize the potential operative risks
involved in these procedures.
Technical Approach: This is a 4-hour afternoon laboratory session. The LARS, under the
supervision of an attending veterinarian, will administer the anesthesia. During this time, 3 pigs
will be anesthetized under general anesthesia using IM Rompun/ketamine (2.2mg/kg 20mg/kg).
LARS will then obtain intravenous access. Once an adequate plan of anesthesia has been reached,
the course participants will perform rigid and flexible bronchoscopy with extraction of a foreign
body and esophagoscopy under the supervision of an attending endoscopist. In order to maximize
the number of procedures that can be performed within the shortest amount of anesthetic
exposure, three live animal stations will be used. The first and second station will be used to teach
rigid endoscopy and foreign body removal. The third station will be used to teach flexible
endoscopy and foreign body removal. There will also be two additional teaching stations. One will
involve instrument set up and use, while the other will involve a teaching station for removal of a
safety pin.
Approximately 20 endoscopic procedures will be performed on each animal. Foreign bodies
will be used that reproduce those encountered in clinical practices (peanuts, beans, Lego). The
foreign bodies will be endoscopically placed and extracted from the bronchus and trachea, under
direct vision of the participants and instructors. At the end of the laboratory session, the pigs will
be euthanized while they are still under general anesthesia in accordance with the IAW LARS
SOP for euthanasia.
All course participants will perform bronchoscopies and foreign body removal on models
prior to operating on the swine. The course participants will also participate in a half-day didactic
component prior to the laboratory session and will be required to undergo a post course quiz.
Completion of the training will be determined by the participant's ability to successfully, and
atraumatically perform a bronchoscopy and esophagoscopy with airway foreign body removal.
Progress: Protocol is expired Oct 2005, no labs done in FY 06. New protocol submitted and
approved to continue this training.
472
Detail Summary Sheet
Date: 30 Sep 06 Number: 206030 Status: Ongoing
Title: Pediatric Bronchoesophagology Laboratory using Swine (Sus scrofa)
Principal Investigator: LTC Douglas M. Sorensen, MC
Department: Surgery/Otolaryngology Facility: MAMC
Associate Investigator(s): None.
Start - Completion: Funding: Periodic Review:
3/8/2006 - Dec 2008 DCI N/A
Study Objective: Skills used to remove foreign bodies in the airway or the esophagus are difficult
to develop, taking years of training. To enhance and perfect these skills one must practice. This is
best done in a laboratory setting with animal models. A laboratory allows the student to become
familiar with the equipment used in pediatric endoscopy and reduplicates the real life setting
closely. This ensures a level of technical proficiency that would enable the student to safely and
successfully perform endoscopy and endoscopic procedures on children.
Technical Approach: Training Design: Animals, usually swine, are fully anesthetized by the
certified veterinarian and his assistants. Under the supervision and instruction of board certified
staff Otolaryngologists, bronchoesophagology procedures are performed on the animals by the
residents. Procedures include direct laryngoscopy, rigid bronchoscopy, rigid esophagoscopy, and
endoscopic removal of foreign bodies. The animals are sacrificed after all residents have completed
training in the procedures.
Anticipated Outcome: Increased proficiency in broncho-esophagology procedures. The junior
resident is better prepared to actually perform these procedures in pediatric patients. The more
experienced residents are able to sharpen their proficiency on pediatric broncho-esophagology.
Clinical Application: The more experienced residents are able to sharpen their proficiency in
pediatric broncho-esophagology. The junior resident is better prepared to actually perform these
procedures in pediatric patients.
Progress: This training protocol was updated and submitted for IACUC approval during FY06.
No training labs were held during FY06. A training lab is planned for FY07.
473
Detail Summary Sheet
Date: 30 Sep 06 Number: 204070 Status: Ongoing
Title: Perioperative Immunonutrition in Head and Neck Cancer
Principal Investigator: LTC Douglas M. Sorensen, MC
Department: Surgery/Otolaryngology Facility: MAMC
Associate Investigator(s): Mary S. McCarthy, RN, PhD; MAJ Brian J. Baumgartner, MC; LTC
Susan G. Smith, AN; CPT Katherine A. Simonson, AN; Vincent D. Eusterman, MD; CPT Sean
M. Demars, MC; Evelyn B. Elshaw, RD, MS
Start - Completion: Funding: Periodic Review:
7/20/2004 - Oct 2005 Triservice Nursing Research Program via The 4/25/2006
Geneva Foundation
Study Objective: (1) To determine the feasibility of providing perioperative nutritional support to
a convenience sample of undernourished adults undergoing surgery for head and neck cancer. (2)
To compare the difference in the nutritional parameters, albumin and prealbumin, between adult
patients receiving IEN support or standard nutrition support administered before and after
surgery for head and neck cancer. (3) To compare the difference in immune response measured by
cutaneous delayed-type hypersensitivity testing, lymphocyte counts, and lymphocyte subset counts
between adult patients randomized to receive either IEN support or standard nutrition support
administered before and after surgery for head and neck cancer. (4) To compare the difference in
surgical wound healing measured by visual inspection between adult patients randomized to
receive either IEN support or standard nutrition support administered before and after surgery for
head and neck cancer.
Technical Approach: On the day that consent is obtained demographic information will be
recorded for age, gender, height, weight, diagnosis, risk factors, tumor category, and prior
radiation therapy. Also, subjects will complete their section of the subjective global assessment
(SGA) tool. Body fat analysis, indirect calorimetry (IC), and dietitian (RD) consultation will be
performed. The speech language pathologist (SEP) will also examine the patient briefly to
determine if any oral intake is safe. Subjects meeting criteria for inclusion into the study will be
randomized to the experimental or control feeding group by the Research Associate.
Once the consent form is signed the surgery date will be noted and the first home visit will be set
up with the patient for 8 days prior to surgery. Subjects will have baseline laboratory tests
(albumin, prealbumin, T & B lymphocytes, and lymphocyte subsets) drawn on Day-8 or prior to
initiating feedings (such as during the preoperative workup). A delayed cutaneous hypersensitivity
test will also be placed by the immunization clinic prior to initiating the protocol. During the first
home visit, any teaching given by the nursing staff regarding the feeding tube in the hospital will
be reinforced and the RA will demonstrate proper use and care of the feeding device. The schedule
for feedings (both oral and by feeding device) will also be reviewed with study groups. The RA will
distribute the formula to all subjects when making the first home visit. Subjects will receive
enough formula to administer >1 liter each day for 7 days. Containers will be labeled with the day
and suggested time for infusion as well as numbered for accountability. The RA will also provide
each subject with a diary. This diary will be used to record reasons for not following the feeding
protocol, gastrointestinal symptoms, feelings/emotions, or questions to ask the investigators.
Each day for the next 6 days of preoperative feeding the RA will phone the subject and ask about
adherence to the feeding protocol, difficulties with the feeding tube, or general concerns. Subjects
will be reminded to save all formula containers and to bring them to the hospital the day of
surgery. Postoperative follow-up visits occur with the ENT surgeon on a weekly basis. These visits
will provide the perfect forum for the multidisciplinary research team to meet with the patient and
474
assist with any care issues that have developed since discharge. On POD 15, 22, and 29, a wound
healing assessment will be performed by the physician and nurse jointly. On POD 29 the subject
has completed the interventional study period and the PI/RA will record data regarding hospital
outcomes, wound healing outcomes, and infectious complications.
Progress: This protocol has closed to enrollment, with fifteen patients enrolled who completed the
study. Data analysis is ongoing. Perioperative nutrition support was found to be feasible and
favorably accepted by patients and staff. Subjects did not vary in demographics at baseline.
Preliminary analyses suggest a trend of less immune suppression (measured by CD4, CD8, and
CD4:8 ratio) in the treatment group (TG) who received immune-modulating nutrition support for
seven days pre- and post-operatively compared to the control group who received standard
nutrition support. Patients were followed for three-weeks postoperatively to assess wound healing
and infectious complications. No adverse events occurred during the study.
475
Detail Summary Sheet
Date: 30 Sep 06 Number: 206057 Status: Ongoing
Title: Review of Thyroid Cancer Treatment Outcomes at a Major Medical Center from 1996-
2000
Principal Investigator: CPT Samuel A. Spear, MC, USAF
Department: Surgery/Otolaryngology Facility: MAMC
Associate Investigator(s): LTC Douglas M. Sorensen, MC
Start - Completion: Funding: Periodic Review:
1/31/2006 - Jan 2007 DCI N/A
Study Objective: This will be a retrospective chart review of patients diagnosed with thyroid
cancer at Madigan Army Medical Center from 1996 to 2000 to determine the effect of clinical and
treatment factors on local tumor control, control of distant metastasis, recurrence, survival, and
complications in all patients diagnosed and treated with differentiated thyroid carcinoma.
Technical Approach: All the records of patients diagnosed and treated for thyroid carcinoma at
Madigan Army Medical Center from 1996-2000 will be identified through the MAMC pathology
database, MAMC tumor-registry records and MAMC outpatient medical records and reviewed.
Individual patient data will be collected with regards to age at diagnosis, gender, ethnicity, date of
last known follow-up, initial FNA result, the presence of positive lymph nodes or metastases, the
staging at diagnosis, the original tumor size, the histological type, the surgical treatment, any
adjuvant therapy, any complications, recurrence date and location, treatment of the recurrence,
mortality, cause of death, & disease free period. Data will be entered into an Excel spreadsheet for
further evaluation and analysis.
Progress: Medical records of patients newly diagnosed and treated for thyroid cancer at Madigan
Army Medical Center (MAMC) from 1996-2000 were identified and examined. Eighty-two (82)
patients were identified as being treated for new onset thyroid carcinoma at this medical facility
from 1996-2000, of which all were eligible for review. Initial review and statistical analysis is
complete. Results were presented as a poster presentation at the Madigan Army Medical Center
Research Day in May 2006, and also presented at the 2006 AAO-HNSF Annual Meeting and at the
OTO EXPO in Toronto, California, September 2006. The protocol remains ongoing to conduct the
final statistical analysis, along with a paper submission to a medical journal.
476
Detail Summary Sheet
Date: 30 Sep 06 Number: 205009 Status: Ongoing
Title: Inferior Turbinate Reduction Comparing Turbinate Microdebrider, Coblation and Bipolar
Cautery
Principal Investigator: CPT Roy F. Thomas, MC
Department: Surgery/Otolaryngology Facility: MAMC
Associate Investigator(s): CPT Jamie Hanson, MC; CPT Matthew R. Grafenberg, MC
Start - Completion: Funding: Periodic Review:
3/11/2005 - Apr 2006 Arthrocare via Geneva Foundation 10/26/2006
Study Objective: To determine the efficacy of inferior turbinoplasty using three accepted
methods: turbinate microdebrider, coblation or submucous diathermy.
Technical Approach: This is a prospective, single blinded, randomized trial to compare use of a
turbinate microdebrider, coblation and bipolar cautery device to determine if use of the
microdebrider or coblator results in increased nasal volumes, decreased symptom scores and
decreased nasal crusting when compared with turbinate bipolar. 90 patients, 30 per arm, will be
recruited from patients referred to ENT with complaints of nasal obstruction. After informed
consent is obtained, baseline evaluations will include history and physical exam, rhinoscopy,
acoustic rhinometry and symptom scores. Patients will be randomized to receive turbinate
reduction via turbinate microdebrider, coblator or bipolar. Follow up examinations will take place
at 1 week, 2 weeks, 1 month and three months. Nasal crusting will be graded at 1 week, 2 weeks
and 1 month. Symptom scores, rhinoscopy and acoustic rhinoscopy will be performed at 3 and 6
months. Comparisons will be made between baseline and postoperative data and between
treatment groups. Results in change of volume from acoustic rhinometry will be evaluated with
ANOVA to compare change in volume between the three arms of the study. Change in symptom
scores between the three arms will be compared with the Kruskal Wallis test.
Progress: This protocol remains ongoing; however, enrollment was delayed by approval of
coblator machine for use in OR. Has since been cleared by CJA and all needed equipment is ready,
staff are trained, and enrollment can commence. Study is still pertinent and numbers should
accumulate rapidly.
477
Detail Summary Sheets
Urology Service, Department of Surgery
478
Detail Summary Sheet
Date: 30 Sep 06 Number: 205129
Status: Terminated
Title: A Multi-Center, Open-Label Evaluation of the Safety of Silodosin in
Signs and Symptoms of Benign Prostatic Hyperplasia, Protocol #SI040011
Principal Investigator: MAJ Karen C. Baker, MC
the Treatment of the
Department: Surgery/Urology
Facility: MAMC
Associate Investigator(s): COL Robert C. Allen, MC; MAJ Keith J. O'Reilly, MC; MAJ Andrew
C. Peterson, MC
Start - Completion: Funding:
1/9/2006 - Jul 2006 Watson Laboratories, Inc. via The Geneva
Foundation
Periodic Review:
N/A
Study Objective: The primary objective is to evaluate the safety of silodosin 8 mg given once
daily for 40 weeks as measured by adverse events, vital signs, electrocardiograms, clinical
laboratory tests, and physical examination. The secondary objective is to evaluate the sustained
efficacy of silodosin 8 mg given once daily for 40 weeks for the relief of the signs and symptoms of
benign prostatic hyperplasia as measured by changes in score of the International Prostate
Symptoms Score- 1 and maximum urine flow rate.
Technical Approach: This is a multi-center, open-label 40 week investigation of up to 1200 men
with signs and symptoms of BPH. This study will serve as an open-label extension for BPH
patients who have previously completed a 12-week double-blind investigation of silodosin (SI04009
or SI04010), with Visit 1 of this study occurring on the same day as the last visit of the double¬
blind study. Note that some data from the previous double-blind study (demographics, medical and
medication history from Visit 1, and physical examination, ECG, clinical labs, vital signs, IPSS-1,
Qmax, concomitant medication from Visit 8) will be carried over for this study. Silodosin 8 mg once
daily with food at breakfast will be administered each day. Seven visits will occur at weeks 0, 2, 8,
16, 24, 32, and 40 or discharge. Informed consent will be obtained at Visit 1. A physical exam will
be performed at visit 7 or discharge. ECGs will be obtained at Visits 3 and 7 or discharge. Clinical
laboratory tests will be performed at Visits 3, 4, and 7 or discharge. Vital signs will be performed
at Visits 3, 4, and 7 or discharge. The IPSS-1 questionnaire will be administered at Visit 3 and 7 or
discharge. Measurements of Qmax will occur at Visits 3 and 7 or discharge. Adverse events will be
monitored at every visit after drug dispensing. Concomitant medications will be monitored at
every visit. Investigational product compliance will be reviewed at all visits after drug dispensing.
Progress: The study sponsor terminated this protocol as of 27 June 2006, and will not be
completing a study close out visit since MAMC was never activated as a study site and no patients
were enrolled.
479
Detail Summary Sheet
Date: 30 Sep 06 Number: 205092
Status: Ongoing
Title: A Multi-center, Randomized Clinical Investigation of TrelstarTM Versus Continued
Therapy in Patients Receiving Lupron or Zoladex for Advanced Prostate Cancer
Principal Investigator: MAJ Karen C. Baker, MC
Department: Surgery/Urology
Facility: MAMC
Associate Investigator(s): COL Robert C. Allen, MC; MAJ Keith J. O'Reilly, MC; MAJ Andrew
C. Peterson, MC
Start - Completion: Funding:
10/27/2005 - Jul 2007 Pharmatech, Inc. via Henry M. Jackson
Foundation
Periodic Review:
7/20/2006
Study Objective: Primary Objective: to compare the inhibitory effect of TrelstarTM versus
Lupron or Zoladex on serum testosterone level in patients with advanced prostate cancer.
Secondary Objectives: (1) To compare the degree of testosterone suppression by Trelstar TM versus
Lupron or Zoladex, (2) To compare the safety and tolerability of TrelstarTM therapy versus
Lupron or Zoladex therapy, and
Technical Approach: Male patients from the Department of Urology who are currently receiving
hormonal therapy for advanced prostate cancer will be offered this research protocol. Subjects will
be randomized in a 1:1 ratio to either continuation with current therapy (Lupron or Zoladex) or to
study drug (Trelstar), given on a monthly or every three month basis depending on their current
treatment schedule. Response will be measured with laboratory tests for testosterone and PSA,
and adverse event recording at Baseline and Day 85. Adverse events will be compared with respect
to number and severity of events. 95% confidence intervals will be computed for the differences
between the Trelstar group and the Continuing therapy group.
Progress: This protocol remains open to enrollment with no subjects screened or consented during
FY06.
480
Detail Summary Sheet
Date: 30 Sep 06 Number: 205072 Status: Completed
Title: A Multi- Center, Randomized, Double-Blind, Placebo Controlled, Parallel Evaluation of the
Efficacy and Safety of Silodosin in the Treatment of the Signs and Symptoms of Benign Prostatic
Hyperplasia, Protocol # SI04009
Principal Investigator: MAJ Karen C. Baker, MC
Department: Surgery/Urology
Facility: MAMC
Associate Investigator(s): COL Robert C. Allen, MC; MAJ Keith J. O'Reilly, MC; MAJ Andrew
C. Peterson, MC
Start - Completion: Funding:
7/8/2005 - Apr 2006 Watson Laboratories, Inc. via The Geneva
Foundation
Periodic Review:
4/25/2006
Study Objective: Primary objective: The primary objective of the trial is to test the hypothesis
that the effectiveness of silodosin 8 mg given once daily for 12 weeks is superior to placebo for the
relief of symptoms of benign prostatic hyperplasia as measured by a baseline to endpoint change in
the total score of the International Prostate Symptoms Score- l(IPSS-l). Secondary objectives. (2)
To test the hypothesis that the effectiveness of silodosin is superior to placebo based on a baseline
to endpoint change in the maximum urine flow rate (Qmax). (2) To compare the safety of silodosin
to placebo using an evaluation of adverse events, vital signs, ECGs, clinical laboratory tests, and
physical exams.
Technical Approach: This is a multicenter, double-blind, placebo controlled, parallel, 12 week
treatment trial in a sufficient number of men with signs and symptoms of BPH, such that 600 are
randomized. Screening will occur within 4 weeks of Visit 1. A 4-week single-blind placebo run-in
period will be followed by 12 weeks of therapy with silodosin 8 mg, or placebo, once daily with food
at breakfast. Nine visits will occur at screening and weeks -4, -2, 0, 0.5, 1, 2, 4, and 12 or
discharge. Informed consent will be obtained at screening. A physical exam will be performed at
Visits 1 and 8 or discharge. ECGs will be obtained at Visits 1, 7, and 8, or discharge. Clinical
laboratory tests will be performed at screening and Visits 1, 7, and 8 or discharge. Vital signs will
be performed at Visits 1, 3, 7, and 8 or discharge, with an orthostasis test being included on Visits
1, and pre- and post-dose on Visit 3. The IPSS-1 questionnaire will be administered at each visit to
the clinic after screening, including an additional test being completed over the telephone 3 days
after Visit 1 while the patient is available to conduct a candid phone conversation. Measurements
of Qmax will occur at Visits 1, 2, 3, (pre- and 2-6 hours post-dose), 5, 6, 7, and 8 or discharge. A
plasma sample for the pharmacokinetic analysis of silodosin and major metabolites will be
obtained at Visits 3 (2-6 hours after first dose) and 7 (2 to 6 hours post-dosing). Adverse events will
be monitored at every visit after drug dispensing (including placebo). Concomitant medications
will be monitored at every visit. Investigational product compliance will be reviewed at all visits
after drug dispensing.
Progress: A study site close out visit was conducted in June 2006. Seven MAMC subjects were
screened; two were randomized and completed the study. Four subjects did not meet
randomization criteria and were withdrawn and one subject failed screening. No internal adverse
events were reported.
481
Detail Summary Sheet
Date: 30 Sep 06 Number: 203035
Status: Ongoing
Title: A Multi- Institutional Pilot Study to Evaluate Molecular Markers
the Early Detection of Prostate Cancer
in Urine and Serum in
Principal Investigator: MAJ Karen C. Baker, MC
Department: Surgery/Urology
Facility: MAMC
Associate Investigator(s): MAJ Keith J. O'Reilly, MC; MAJ Raymond S. Lance, MC; CPT Jack
R. Walter, MC
Start - Completion: Funding:
2/28/2003 - Nov 2003 NCI
Periodic Review:
1/18/2006
Study Objective: The primary objective of this study is to examine whether the presence of
tumor- specific gene promoter hypermethylation (e.g., GSTP1, Annexin II, CD44 and Caveolin 1) in
serum and/or urine sediments can predict prostate cancer among patients referred to diagnostic
biopsy. The secondary objective of this study is to explore whether the presence of tumor- specific
gene methylation (e.g., GSTP1, Annexin II, CD44 and Caveolin 1) in core-needle biopsy specimens
can predict subsequent disease status in patients who biopsy negative and develop cancer on
subsequent biopsy within two years.
Technical Approach: 50 men who are between the ages of 40 and 75 years old and require
prostate core needle biopsy will be enrolled in this pilot study here at MAMC. At the biopsy visit
prior to the procedure the patient will be asked to provide a serum specimen. A 15-30 second
prostate massage will be conducted and patients will be asked to provide a 30-50 ml urine
specimen within 30 minutes of the massage. Each patient will undergo their scheduled core needle
biopsy of the prostate. The number of biopsy cores taken will range from 8-12 which is Standard of
Care at MAMC and will be left up to the discretion of the doctor performing the study. The
concordance between gene methylation in the serum and urine, and diagnostic biopsy will be
determined for all patients. Also methylation status of the tumor specimen will be determined for
all cases who receive curative radical prostatectomy. Follow-up with patients will be determined
by biopsy results. Length of study follow-up will be five years.
Progress: This protocol closed to enrollment with 100 patients enrolled, none during FY06. Follow
up clinical data will be collected from the study participants for the next five years. Methylation
assay of three genes in question has been completed on the biopsy cores of all 100 patients. The
analysis of the urine samples is ongoing.
482
Detail Summary Sheet
Date: 30 Sep 06 Number: 201113 Status: Ongoing
Title: A Phase III, Extension Study to Evaluate the Safety of 10 mg Atrasentan in Men with
Hormone-Refractory Prostate Cancer (MOO-258)
Principal Investigator: MAJ Karen C. Baker, MC
Department: Surgery/Urology Facility: MAMC
Associate Investigator(s): MAJ Andrew C. Peterson, MC; CPT Jennifer M. Pugliese, MC; ;
MAJ Michael J. Sebesta, MC; MAJ Keith J. O'Reilly, MC; COL Robert C. Allen, MC
Start - Completion: Funding: Periodic Review:
9/4/2001 - Jul 2002 Abbott Labs via The Geneva Foundation 5/23/2006
Study Objective: To evaluate the safety of 10 mg Atrasentan for the treatment of prostate
cancer. In addition, the pharmacokinetic parameters of Atrasentan will be defined in a sub¬
population of subjects.
Technical Approach: This is a phase III, open label study evaluating the safety of 10 mg
Atrasentan in men with hormone refractory prostate cancer. All men enrolled in this protocol must
have successfully met all of the eligibility criteria for this trial and have completed one of the
following Phase III trials:
MOO-211: A Phase III, Randomized, Double-Blind, Placebo controlled Study Evaluating the Safety
and Efficacy on 10 mg Atrasentan in Men with Metastatic, Hormone-Refractory Prostate Cancer
MOO-244: A Phase III, Randomized, Double-Blind, Placebo Controlled Study Evaluating the Safety
and Efficacy of 10 mg Atrasentan in Men with Non-Metastatic Hormone Refractory Prostate
Cancer
Eligible men will receive a single, oral dose (soft gelatin capsule) of 10 mg Atrasentan before
leaving the clinic (Day 1). They will then continue taking the same dose of study drug once a day
at approximately the same time each day. The study participants will be asked to return to the
clinic on study days 14, 28, at Week 12, and then every 12 weeks thereafter. Upon study
completion subjects will be asked to come into the clinic for a final assessment, and will return
again for a safety evaluation 30 days after the last dose of study drug. Blood will be drawn at every
visit. Urine samples will be obtained at visit Day 1, Day 28, every 12 weeks and at final visit.
Progress: This is an extension protocol to study #201121. Six patients enrolled overall at MAMC,
one during FY06. Four patients completed the study, one patient was discontinued and one patient
remains active. The protocol is now closed to patient entry.
483
Detail Summary Sheet
Date: 30 Sep 06 Number: 201107 Status: Ongoing
Title: A Phase III, Randomized, Double-Blind, Placebo-Controlled Study of the Safety and
Efficacy of 10 mg Atrasentan in Men with Metastatic, Hormone-Refractory Prostate Cancer
(MOO-211)
Principal Investigator: MAJ Karen C. Baker, MC
Department: Surgery/Urology Facility: MAMC
Associate Investigator(s): MAJ Andrew C. Peterson, MC; CPT Jennifer M. Pugliese, MC; MAJ
Keith J. O'Reilly, MC; MAJ Henry E. Ruiz, MC; CPT Jack R. Walter, MC; MAJ Leah P.
McMann, MC; MAJ Sunil K. Ahuja, MC; MAJ Thomas L. Poulton, MC; COL Raymond A.
Costabile, MC; MAJ Raymond S. Lance, MC; COL Robert C. Allen, MC
Start - Completion: Funding: Periodic Review:
9/4/2001 - Jul 2002 Abbott Labs via The Geneva Foundation 6/8/2006
Study Objective: 1) To evaluate the safety and efficacy as measured by time-to-disease
progression. 2) To evaluate the effect of 10 mg Atrasentan on: PSA progression, Biochemical bone
markers, Bone scan index, Survival and to evaluate the effect of the study drug on quality of life
and performance status and to perform population pharmacokinetic analysis.
Technical Approach: This is a phase III, multicenter, multinational trial evaluating the safety
and efficacy of 10 mg Atrasentan in men with metastatic, hormone refractory prostate cancer. The
men participating in this study have been diagnosed with hormone-refractory prostate cancer that
has been treated with surgical and/or chemical castration but is now escaping androgen
suppression as demonstrated by rising PSA. There must also be evidence of distant metastasis.
The patient will then enter the screening phase, which will last £ 35 days and will include EKG,
laboratory tests, medical history and physical examination. CT scan (or MRI) & bone scan will be
performed. A copy of all scans will be sent to a Central Imaging Center within 2 weeks of
collection. The patient will be randomized in a 1:1 ratio to receive either Atrasentan or a placebo
(Day 1) via an Interactive Voice Response System (IVRS). Participants will be assigned a 4-digit
study number and will be given study drug prior to leaving the clinic. Study medication will then
be taken once a day at approximately the same time each day except for at Weeks 4 & 12 when a
trough blood specimen will need to be drawn. At those two visits the patient will take the study
medication after all laboratory specimens have been drawn. Participants will visit the clinic on
Day 14, Weeks 4, 8, & 12, and every 6 weeks thereafter. At each visit the participants will be
assessed for safety, clinical evidence of disease progression and will be dispensed study medication.
They will be evaluated for disease progression by radiographic imaging every 12 weeks and as
needed if participant experiences symptoms suspected to be related to disease progression. The
subject will be considered to have completed the study if he has experienced an event of disease
progression that has been confirmed by an independent reviewer, or is active in the trial when the
double-blind treatment period ends (as defined by when 650 subjects have experienced confirmed
events of disease progression). The subject will then be eligible to enter the open label extension
study. If he declines to participate in the extension study, he will be asked to return for safety
evaluation 30 days after their final visit. Subjects will be assessed for post-treatment survival at 3-
month intervals after the last study visit. Someone who did not complete the study (premature
withdrawal) will not be eligible to enter the extension study, but will be asked to continue coming
in for visits as outlined above.
Progress: This study closed to patient entry in February 2003, with eight subjects screened, six
randomized, four who completed the study, one screen failure and one who withdrew consent. Four
internal serious adverse events were reported during the active study period. There are no
484
patients continuing to be followed under this protocol. The study remains ongoing at MAMC
pending a formal site close out visit with the study sponsor.
485
Detail Summary Sheet
Date: 30 Sep 06 Number: 201121 Status: Ongoing
Title: A Phase III, Randomized, Double-Blind, Placebo-Controlled Study of the Safety and
Efficacy of 10 mg Atrasentan in Men with Non-Metastatic, Hormone-Refractory Prostate Cancer
(MOO-244)
Principal Investigator: MAJ Karen C. Baker, MC
Department: Surgery/Urology Facility: MAMC
Associate Investigator(s): MAJ Andrew C. Peterson, MC; CPT Jennifer M. Pugliese, MC; MAJ
Keith J. O'Reilly, MC; COL Robert C. Allen, MC
Start - Completion: Funding: Periodic Review:
10/11/2001 - Sep 2002 Abbott Labs via The Geneva Loundation 6/27/2006
Study Objective: Primary: To evaluate the safety and efficacy as measured by time-to-disease
progression.
Secondary: (1) To evaluate the effect of 10 mg Atrasentan on: PSA progression, Biochemical bone
markers, Bone scan index, (2) Survival, (3) To evaluate the effect of the study drug on quality of
life and performance status and (4) To perform population pharmacokinetic analysis.
Technical Approach: This is a phase III, multicenter, multinational trial evaluating the safety
and efficacy of 10 mg Atrasentan in men with metastatic, hormone refractory prostate cancer. The
men participating in this study have been diagnosed with hormone-refractory prostate cancer that
has been treated with surgical and/or chemical castration but is now escaping androgen
suppression as demonstrated by rising PSA. There must also be evidence of distant metastasis.
The patient will then enter the screening phase, which will last less than or equal to 35 days and
will include EKG, laboratory tests, medical history and physical examination. CT scan (or MRI) &
bone scan will be performed. A copy of all scans will be sent to a Central Imaging Center within 2
weeks of collection. After the patient has met eligibility criteria, the patient will be randomized in
a 1:1 ratio to receive either Atrasentan or a placebo (Day 1) via an Interactive Voice Response
System (IVRS). Study medication will then be taken once a day at approximately the same time
each day except for at Weeks 4 & 12 when a trough blood specimen will need to be drawn. At those
two visits the patient will take the study medication after all laboratory specimens have been
drawn. The subject will be considered to have completed the study if he has experienced an event
of disease progression that has been confirmed by an independent reviewer, or is active in the trial
when the double-blind treatment period ends. The subject will then be eligible to enter the open
label extension study. If he declines to participate in the extension study, he will be asked to
return for safety evaluation 30 days after their final visit. Subjects will be assessed for post¬
treatment survival at 3-month intervals after the last study visit. Someone who did not complete
the study (premature withdrawal) will not be eligible to enter the extension study, but will be
asked to continue coming in for visits as outlined above.
Progress: This protocol closed to patient entry 31 March 2003, with nine patients enrolled at
MAMC. Seven patients completed the clinical trial and two patients withdrew consent. Two
patients have been rolled over into the (M00-258) extension trial within the last 12 months. There
are currently no patients on active study medication, but continue to receive survival status follow¬
up calls.
486
Detail Summary Sheet
Date: 30 Sep 06 Number: 204005 Status: Ongoing
Title: A Phase III, Randomized, Double-Blind, Placebo-Controlled Trial Evaluating the Ability of
Risedronate to Prevent Skeletal Related Events in Patients with Metastatic Prostate Cancer
Commencing Hormonal Therapy, Protocol #GU02-41
Principal Investigator: MAJ Karen C. Baker, MC
Department: Surgery/Urology Facility: MAMC
Associate Investigator(s): MAJ Andrew C. Peterson, MC; ; MAJ Michael J. Sebesta, MC; MAJ
Jasmine T. Daniels, MC; ETC David E. McCune, MC; MAJ Angela G. Mysliwiec, MC; CPT
Jennifer M. Pugliese, MC; MAJ Keith J. O'Reilly, MC; COL Robert C. Allen, MC
Start - Completion: Funding: Periodic Review:
1/29/2004 - Oct 2004 Hoosier Oncology Group via The Geneva 10/24/2006
Foundation
Study Objective: (1) To evaluate the ability of a daily oral dose of 30 mg risedronate as compared
with placebo to prevent skeletal complications in patients undergoing androgen deprivation for
metastatic prostate cancer by measuring the time to a skeletal-related event (SRE). (2) T evaluate
a daily oral dose of 30 mg risedronate compared to placebo in patients undergoing androgen
deprivation for metastatic prostate cancer with respect to the following: (a) The rate and the
duration of the serological response by measuring the changes in prostate- specific antigen (PSA)
levels, (b) The effect on tumor response by measuring the response rate after 6 months of therapy
by radiographic means, (c) Time to development of hormone refractory disease, (d) The changes in
biochemical markers of bone turnover, (e) Overall survival, (f) The safety and the tolerability as
determined by frequency and severity of treatment-emergent adverse events.
Technical Approach: This is a randomized, placebo-controlled, double-blind, multicenter,
stratified, 2-arm study. Up to 360 evaluable subjects will be enrolled at approximately 50 study
sites. After stratification based on age, performance status, and severity of metastatic disease,
subjects will be randomized at a 1:1 ratio to the following treatment arms: (a) Daily risedronate
combined with androgen deprivation, and (b) Daily oral placebo combined with androgen
deprivation The study population will consist of prostate cancer subjects with metastatic bone
disease for whom androgen- deprivation therapy is planned. Subjects will be registered to the study
within 3 days before beginning risedronate or placebo and may begin androgen-deprivation
therapy 7 days before beginning risedronate or placebo. The subject will receive treatment of one
30-mg tablet/placebo oral per day every morning. Subject is to take risedronate/placebo with 6-8 oz
of water 30 minutes before the first food or drink of the day and should not lie down for 30 minutes
after taking. Subjects will receive concomitant treatment with calcium carbonate at a dose of at
least 500 mg orally per day every evening. Subjects will receive concomitant treatment with
vitamin D at a dose of at least 400 IU. Subjects will remain in the study for at least 12 weeks, but
may continue for 2 years or longer depending on progression of disease. They will be seen in the
clinic every 4 weeks for the first 12 weeks and every 12 weeks thereafter.
Progress: This protocol is closed to enrollment with four patients enrolled. One patient has been
lost to follow-up and one patient remains active on study treatment. The other patients continued
to be followed during FY06.
487
Detail Summary Sheet
Date: 30 Sep 06 Number: 204122 Status: Completed
Title: A Randomized, Double Blind, Placebo Controlled, Four Arm (Placebo, Tolterodine ER,
Tamsulosin, and Tolterodine ER plus Tamsulosin) Study to Evaluate the Clinical Efficacy and
Safety of Tolterodine ER 4 mg in Men who have Frequency and Urgency, with or without
Urinary Urge Incontinence, with or without Bladder Outlet Obstruction, Protocol Number
A6121120
Principal Investigator: MAJ Karen C. Baker, MC
Department: Surgery/Urology Facility: MAMC
Associate Investigator(s): COL Robert C. Allen, MC; MAJ Andrew C. Peterson, MC; MAJ
Keith J. O'Reilly, MC; CPT Brian J. DeCastro, MC
Start - Completion: Funding: Periodic Review:
12/2/2004 - Sep 2005 Pfizer via The Geneva Foundation 9/27/2005
Study Objective: Primary objective of the trial is to evaluate the effect of tolterodine ER plus
tamsulosin versus placebo on patient perception of overall treatment benefit in men who have
frequency and urgency, with or without urinary urge incontinence (UUI), with or without bladder
outlet obstruction (BOO). Secondary objective is to evaluate the effect of, Tolterodine ER vs.
placebo, Tolterodine ER plus tamsulosin vs. tamsulosin, Tolterodine ER plus tamsulosin vs.
tolterodine ER, Tamsulosin vs. placebo, and Tamsulosin vs. tolterodine ER on efficacy, safety,
patient's perception, health-related quality of life and sexual function in men who have frequency
and urgency, with or without UUI, with or without BOO.
Technical Approach: This is a 12-week randomized, double blind, placebo controlled, four arm
(placebo, tolterodine ER, tamsulosin, and tolterodine ER plus tamsulosin) multicenter, United
States study to evaluate the effects of tolterodine in men who have frequency and urgency, with or
without UUI, with or without BOO. 830 adult male subjects, > 50 years of age, will be enrolled in
this study. The trial will be conducted at 83 centers with each center enrolling 10 subjects. All
subjects will be equally randomized (1:1: 1:1) into four groups and will receive placebo, tolterodine
ER, tamsulosin, or tolterodine ER plus tamsulosin once a day for 12 weeks. Each group will receive
either: Tolterodine ER placebo plus tamsulosin placebo, Tolterodine ER plus tamsulosin placebo,
Tolterodine ER placebo plus tamsulosin, or Tolterodine ER plus tamsulosin. Following consent,
patients will be screened for inclusion criteria. At Baseline/Visit 2 (Day 0), once study entry has
been verified, tests will be performed and study diaries and medication given. Diaries will be
reviewed and survey's completed during Visit 3/Week 1 (Day 7 +2). Study medication will be given
during Visit 4/Week 6 (Day 42 +2). End of Study Visit 5/Week 12 (Day 84 +2) study staff will
review diary, perform tests, and patients will complete surveys. Study staff will complete the
Subject Disposition page. There is no scheduled follow up visit after Visit 5/Week 12.
Progress: This protocol closed enrollment in January 2006 and a study site close out visit was
conducted in July 2006. A total of 23 subjects screened, 16 enrolled, 15 completed and one
withdrew consent prior to completion of the study. Seven subjects screen failed for various reasons.
No internal serious adverse events were reported.
488
Detail Summary Sheet
Date: 30 Sep 06 Number: 206100 Status: Ongoing
Title: A Randomized, Double-Blind, Multicenter Study of Denosumab Compared with Zoledronic
Acid (Zometa®) in the Treatment of Bone Metastases in Men with Hormone-Refractory Prostate
Cancer (20050103)
Principal Investigator: MAJ Karen C. Baker, MC
Department: Surgery/Urology Facility: MAMC
Associate Investigator(s): CPT Jennifer M. Pugliese, MC; ; MAJ Michael J. Sebesta, MC; MAJ
Andrew C. Peterson, MC; CPT Brian J. DeCastro, MC; MAJ Mark I. Anderson, MC; COL Robert
C. Allen, MC; MAJ Keith J. O'Reilly, MC
Start - Completion: Funding: Periodic Review:
9/22/2006 - Jun 2011 Amgen, Inc. via The Geneva Foundation N/A
Study Objective: To determine if denosumab is non-inferior to zoledronic acid (Zometa®) with
respect to the first on-study occurrence of a skeletal-related event (SRE) in men with hormone-
refractory prostate cancer and bone metastases
Technical Approach: This is an international, phase 3, randomized, double-blind, active-
controlled study comparing denosumab with zoledronic acid in the treatment of bone metastases in
men with hormone-refractory prostate cancer. Approximately 1700 subjects will be randomized in
a 1:1 ratio to receive either denosumab, administered at a dose of 120 mg by subcutaneous (SC)
injection every 4 weeks (Q4W), or zoledronic acid, administered at a dose of 4 mg (equivalent
creatinine clearance-adjusted dose in subjects with baseline creatinine clearance > 60 mL/min) by
a single, no less than 15-minute, intravenous (IV) infusion Q4W, in a blinded manner. The
randomization will be stratified by previous SRE (yes or no), PSA level (< 10 ng/mL or > 10
ng/mL), and current (defined as within 6 weeks before randomization) chemotherapy for prostate
cancer (yes or no). Each subject will receive either an SC injection of denosumab and an IV
infusion of zoledronic acid placebo Q4W or an SC injection of denosumab placebo and an IV
infusion of zoledronic acid Q4W. Subjects will continue to receive investigational product Q4W
until 745 subjects have experienced an SRE (defined as pathological fracture [vertebral or non-
vertebral], radiation therapy to bone [including the use of radioisotopes], surgery to bone, or spinal
cord compression). Serum denosumab concentration levels will be obtained from a subset of
approximately 150 subjects at select centers.
Progress: This protocol remains open to patient entry, with no patients enrolled.
489
Detail Summary Sheet
Date: 30 Sep 06 Number: 206072 Status: Ongoing
Title: A Randomized, Double-Blind, Placebo-Controlled, Multi-Center Phase 3 Study of
Denosumab on Prolonging Bone Metastasis-Free Survival in Men with Hormone-Refractory
Prostate Cancer
Principal Investigator: MAJ Karen C. Baker, MC
Department: Surgery/Urology Facility: MAMC
Associate Investigator(s): MAJ Andrew C. Peterson, MC; ; MAJ Michael J. Sebesta, MC; CPT
Jennifer M. Pugliese, MC; COL Robert C. Allen, MC; CPT Brian J. DeCastro, MC; MAJ Mark I.
Anderson, MC; MAJ Keith J. O'Reilly, MC
Start - Completion: Funding: Periodic Review:
6/8/2006 - Mar 2012 Amgen, Inc. via Geneva Foundation N/A
Study Objective: To compare the treatment effect of denosumab with placebo on prolonging bone
metastasis-free survival in men with hormone refractory (androgen independent) prostate cancer
who have no bone metastasis at baseline.
Technical Approach: This is an international, phase 3, randomized, double blind, placebo
controlled study in subjects with hormone refractory (androgen independent) prostate cancer.
Approximately 1400 subjects will be randomized in a 1:1 ratio to receive denosumab at a dose of
120 mg, SC, Q4W or placebo, SC, Q4W. The randomization schedule will be stratified based on
PSA criteria (PSA level 8.0 ng/mL AND PSA doubling time 10.0 months [yes/no]) and previous or
current chemotherapy for prostate cancer (yes/no). Subjects will receive investigational product
until the end of treatment. The treatment period will end after approximately 660 subjects have
developed bone metastasis or died. Subjects will complete the end of study visit approximately 4
weeks after their last dose of investigational product administration. The study duration
(excluding the follow up period) is estimated to be 42 months, which includes an enrollment period
of approximately 15 months.
Progress: This protocol is open to patient entry, with no patients enrolled during FY06. Active
pre-screening for this clinical trial continues.
490
Detail Summary Sheet
Date: 30 Sep 06 Number: 205006 Status: Ongoing
Title: A Randomized, Double-Blind, Placebo-Controlled, Multicenter Efficacy and Safety Study
of Toremifene Citrate for the Prevention of Bone Fractures in Men with Prostate Cancer on
Androgen Deprivation Therapy (Protocol #G300203)
Principal Investigator: MAJ Karen C. Baker, MC
Department: Surgery/Urology Facility: MAMC
Associate Investigator(s): MAJ Andrew C. Peterson, MC; COL Robert C. Allen, MC; MAJ
Keith J. O'Reilly, MC
Start - Completion: Funding: Periodic Review:
1/20/2005 - Jan 2007 GTx, Inc. via The Geneva Foundation 9/26/2006
Study Objective: Primary Objective: To assess the efficacy of toremifene in the prevention of
bone fractures in men with prostate cancer on androgen deprivation therapy as measured by semi
quantitative assessment of vertebral fractures. Secondary Objectives: (1) To assess the safety
profile of toremifene in subjects on androgen deprivation therapy (ADT) for the treatment of
prostate cancer. (2) To assess the effect of toremifene on the incidence of clinical fragility fractures.
(3) To assess the effect of toremifene on bone mineral density (BMD) of the lumbar spine as
assessed by DEXA scan. (4) To assess the effect of toremifene on BMD of the femur as assessed by
DEXA scan. (5) To assess the effect of toremifene on the incidence, frequency and severity of hot
flashes. (6) To assess the effect of toremifene on the incidence and severity of gynecomastia. (7) To
assess the effect of toremifene on quality of life.
Technical Approach: In a double-blind fashion, qualifying subjects will be equally randomized
into one of two treatment groups. Up to 600 subjects will be randomly assigned to receive 60 mg
toremifene citrate as two 40 mg tablets and up to 600 subjects will be randomly assigned to receive
matching placebo tablets containing no toremifene citrate. All treatments will be administered
orally once daily for 24 months. An interim analysis of BMD data will be conducted on the first 200
subjects that complete 12 months of treatment and have baseline and 12 month DEXA
assessments. The treatment duration of the study will be 24 months. The beginning of study
treatment is defined as the first day of toremifene or placebo administration. Subject clinic visits
for this study will include the following: screening, randomization, 3, 6, 9, 12, 15, 18, 21, and 24
months. There will be a screening evaluation including procedures that are necessary to determine
subject eligibility prior to receiving study treatment. The site will contact the subject by telephone
approximately seven days, but no more than ten days, after the randomization visit. The telephone
contact will include assessment of study drug compliance and tolerance. Subsequent phone calls
will be made at monthly intervals +/- 1 week to assess drug compliance and track serious adverse
events. The subject clinic visits will occur every three months for the duration of the study.
Progress: This protocol closed to enrollment with two patients enrolled and randomized at
MAMC. One subject withdrew consent and one subject was discontinued from the study. Both
patients are inactive and no longer receiving treatment. Protocol remains ongoing at MAMC
pending final site close out visit by the study sponsor.
491
Detail Summary Sheet
Date: 30 Sep 06 Number: 204091 Status: Ongoing
Title: A Randomized, Double-Blind, Placebo-Controlled Study to Evaluate AMG 162 in the
Treatment of Bone Loss in Subjects Undergoing Androgen- Deprivation Therapy for Non-
Metastatic Prostate Cancer
Principal Investigator: MAJ Karen C. Baker, MC
Department: Surgery/Urology Facility: MAMC
Associate Investigator(s): MAJ Andrew C. Peterson, MC; CPT Brian J. DeCastro, MC; COL
Robert C. Allen, MC; MAJ Keith J. O'Reilly, MC; CPT Jack R. Walter, MC; Dieter Kirchheim,
MD
Start - Completion: Funding: Periodic Review:
10/5/2004 - Aug 2006 Amgen, Inc. via The Geneva Foundation 5/23/2006
Study Objective: Primary objective is to determine the treatment effect of AMG 162 compared
with placebo on lumbar spine bone mineral density (BMD) in men with non-metastatic prostate
cancer undergoing Androgen Deprivation Therapy. Secondary objectives are to assess the effect of
AMG 162 compared with placebo on the vertebral and non-vertebral fracture incidence, BMD in
total hip and femoral neck and to assess the safety and pharmacokinetics of AMG 162 in this
population.
Technical Approach: This is an international, multi-center, randomized, double-blind, placebo-
controlled study in subjects with non-metastatic prostate cancer undergoing androgen deprivation
therapy (ADT). Approximately 968 subjects at approximately 150 sites in North America and
Europe will be randomly assigned to receive placebo or AMG 162 in a 1:1 allocation ratio. The
randomization schedule will be stratified based on age group (= 70, > 70 years of age), and
duration of ADT with GnRH agonist, or orchiectomy at the time of study entry (0-6 months vs. > 6
months). Subjects will participate in the study for 24 months. There is a planned interim analysis
after subjects complete their one-year (12 month) study evaluation period. Once a subject has been
determined eligible to participate in the study written consent must be obtained prior to screening
for eligibility. Screening assessments include obtaining a medical history, physical examination,
bone scan, radiographs, bone densitometry, and collection of blood for hematology and chemistry.
Eligible subjects will return to the site within 28 days of screening for the baseline (day 1) visit,
during which baseline-related assessments will be done and subjects randomized. Subjects will
return at months 1, 3, 6, 12, 15, 18 and 24 for study related procedures and evaluations. All
subjects will take daily calcium (1 gram) and vitamin D (at least 400 IU). All subjects will receive
the same volume of study medication (AMG 162 vs. placebo) subcutaneously every 6 months. This
study will also explore the effect of AMG 162 on PSA, overall survival, and subject reported
outcomes (subject questionnaires).
Progress: This protocol closed to enrollment with thirteen patients enrolled, none during FY06.
Three patients screen failed and two patients withdrew consent. Eight patients remain on active
study medication and continued to be followed during FY06.
492
Detail Summary Sheet
Date: 30 Sep 06 Number: 204025 Status: Completed
Title: An Evaluation of Semen Characteristics after 40 Weeks Daily Dosing with 20 mg
Tadalafil
Principal Investigator: MAJ Karen C. Baker, MC
Department: Surgery/Urology Facility: MAMC
Associate Investigator(s): COL Raymond A. Costabile, MC; COL Robert C. Allen, MC; MAJ
Keith J. O'Reilly, MC; MAJ Mark I. Anderson, MC; MAJ Andrew C. Peterson, MC
Start - Completion: Funding: Periodic Review:
2/19/2004 - Nov 2004 Lilly via The Geneva Foundation 11/4/2004
Study Objective: (1) To test the null hypothesis that the proportion of subjects who have 50% or
more reduction from baseline in sperm concentration in the tadalafil group is less than 0.20 higher
than that in the placebo group at 40 weeks. (2) To assess the effect of 20 mg tadalafil administered
daily for 40 weeks as compared with placebo on sperm concentration, total sperm number per
ejaculate, sperm motility and sperm morphology. (3) To assess the effect of 20 mg tadalafil
administrated daily for 40 weeks as compared with placebo on serum concentrations of
reproductive hormones testosterone (total and free), LH and FSH. 4) To assess the long term
safety of tadalafil.
Technical Approach: Subjects will include healthy males and males with mild erectile
dysfunction. Subjects will receive either 20 mg tadalafil orally once daily or placebo orally once
daily. During the 4 week screening phase (Visits 1 & 2) subjects will be assigned a unique ID
number for tracking purposes. Ejaculation information will be collected and instructions for 2
semen samples given to subjects. A recall instrument will be given to the subjects to document
each sexual encounter during the course of the study: Global Assessment Questions (GAQ, a one
time assessment of events over the course of the study) and Psychological and Interpersonal
Relationship Scale (PAIRS, a set of scales that assess psychological and relationship aspects of ED
and its treatment). During the 40 week double blind treatment phase (between Visits 2-6) eligible
subjects will be randomly assigned to either placebo or 20 mg tadalafil at Visit 2 and ejaculation
information collected. Visits 3-6 will be scheduled at 12, 22, 32, and 40 weeks from Visit 2, with a
visit window of =/- 7 days. Between Visit 3-6, two semen specimens will be collect from each
subject within at least 48 hours, but no longer than 5 days sexual abstinence prior to each
collection. The two samples will be collected within 1 week on either side of each visit. Early
withdrawal information will be collected and data interpreted. Two more samples will be
requested prior to discontinuation. Reversibility Phase: Up to 26 weeks without study medication
(between Visits 6-8), the reversibility phase may be stopped early as described. Information will be
collected during the 13 weeks between visits and semen specimens collect as above. Subjects who
demonstrate a clinically significant decrease in sperm concentration may be followed after study
completion.
Progress: This protocol was reported completed in November 2005. A final site close-out visit by
the study sponsor was held 3 November 2005. Five subjects enrolled, four screen failed, and one
was randomized and started on the study medication, but became lost to follow-up.
493
Detail Summary Sheet
Date: 30 Sep 06 Number: 205119 Status: Ongoing
Title: Expression of CXCR4 in Archived Prostate Cancer Specimens and its Association with
Patient Demographics, Pathologic Results, and Outcomes
Principal Investigator: MAJ Karen C. Baker, MC
Department: Surgery/Urology Facility: MAMC
Associate Investigator(s): CPT Brian J. DeCastro, MC; LTC Stephen C. Groo, MC; CPT Joren
B. Keylock, MC; CPT Patrick M. McNutt, MS; CPT Jeremy P. Celver, MS; CPT Michael J.
Hartenstine, MS; CPT Garth S. Herbert, MC
Start - Completion: Funding: Periodic Review:
8/15/2005 - Aug 2007 DCI 7/20/2006
Study Objective: Our primary objective is to compare CXCR4 expression in prostate cancer cells
to benign prostate cells in archived prostate specimens. Our secondary objectives are to examine,
to the extent possible, the relationships between CXCR4 expression and patient demographics,
pathological characteristics, and disease specific outcomes.
Technical Approach: This study is a retrospective review of 100-300 patients who underwent
radical retropubic prostatectomy or transurethral resection of the prostate. Pathology specimens
obtained from previous prostatectomies and transurethral resections of the prostate will be stained
for CXCR4 expression with commercially available antibodies and the intensities will be scored
using an ordinal scale as judged by three different investigators. The difference in staining of
cancerous tissue and benign prostatic tissue will be compared with a t-test and a p value of 5% will
be considered statistically significant. These findings will be coordinated with the patients' clinical
course located in outpatient records, CHCS, ICDB, and the CPDR. Differences in CXCR4
expression will be compared to demographic factors such as race and age, and the association with
disease specific outcomes.
Progress: During FY06, this bench protocol has tried several techniques for immunofluorescence
staining for the CXCR4 antigen with mixed and inconsistent results. Investigators are now
attempting colormetric staining techniques.
494
Detail Summary Sheet
Date: 30 Sep 06 Number: 205017 Status: Ongoing
Title: Madigan Army Medical Center Advanced Laparoscopic Training Using the Pig (Sus
scrofa)
Principal Investigator: MAJ Karen C. Baker, MC
Department: Surgery/Urology Facility: MAMC
Associate Investigator(s): COL Kenneth S. Azarow, MC; MAJ James A. Sebesta, MC; MAJ
Alec C. Beekley, MC
Start - Completion: Funding: Periodic Review:
11/10/2004 - Nov 2007 DCI 9/22/2006
Study Objective: Advanced laparoscopic surgical techniques have been developed and are being
used with increased frequency. These include techniques upon the stomach especially anti-reflux
procedures such as the Nissen fundoplication as well as cholecystectomy and exploring the
common bile duct. Laparoscopic techniques for appendectomy, segmental cloectomy, total
colectomy, colostomy creation, abdominoperineal resection, splenectomy and weight loss surgery
have also been developed. The performance of thse procedures requires a higher degree of
laparoscopic training and skills that must be acquired in the laboratory prior to application in the
operating room upon humans, an increased familiarity with these techniques decreases operative
time, continues to train staff and residents and minimizes complications for patients while offering
state of the art and standard of care surgical services.
Technical Approach: To familiarize General Surgery and Urology residents, staff and invited
surgeons from our community with techniques in the performance of advance laparoscopic
techniques. This training will include esophagus, stomach, biliary, small & large intestine, spleen,
liver retroperitoneal and urological procedures. The training benefit will accrue to General
Surgery and Urology residents, Staff and invited surgeons by introducing these techniques or
reinformcing earlier acquired skills in a controlled environment. Familiarity with these
techniques will allow an nicreased margin of safety for patients, decreased operative time and
minimizing of potential complications.
Progress: Protocol is active and training objective are being met. 14 urology residents were
trained in 2 labs and 24 surgery residents were trained in 2 labs.
495
Detail Summary Sheet
Date: 30 Sep 06 Number: 204121
Status: Terminated
Title: Prevalence of PCR Detectable Human Papillomavirus (HPV) in
Comparison of Specimen Collection Methods and Genitourinary Sites
Sexually Active Males - A
Principal Investigator: MAJ Karen C. Baker, MC
Department: Surgery/Urology
Facility: MAMC
Associate Investigator(s): CPT Patrick M. McNutt, MS; MAJ Steven D. Mahlen, MS; LTC
Andrew R. Wiesen, MC; LTC Carol A. Moores, MC; CPT Hieu V. Hoang, MC
Start - Completion: Funding:
1/20/2005 - Oct 2006 DCI
Periodic Review:
2/3/2006
Study Objective: To determine the prevalence of Human Papillomavirus in sexually active males
and compare the sensitivities of different methods of specimen collection at different genitourinary
sites.
Technical Approach: This is a cross-sectional study which plans to enroll 400 subjects. Once
consented, subjects will complete a questionnaire and the investigator will review the
questionnaire to ensure it is completed, examine the subject, collect the specimens, and complete
the data collection sheet. With the exception of the GC/Cz DNA probe, which will be labeled IAW
MAMC laboratory policy, the investigator will label all specimen containers with the subject's
unique code number and the location from which the specimen was obtained.
After collection the specimens will be refrigerated and transported to the DCI within 8 hours. In
the DCI, exfoliated skin specimens will be agitated for 10 minutes and the emery paper and swabs
will be removed. The urine specimen will be centrifuged at 10,000g for 10 minutes and the cellular
debris will be collected and suspended in a buffered saline solution. 150mcl of the solution from the
GC/Cz DNA probe will be pipette into a vial for use in this study and the remainder of the GC/Cz
DNA probe sample will be transmitted to the MAMC laboratory and processed in accordance with
standard operating procedures. The study specimens will be maintained at -70C until further
processing. Subjects with detectable HPV will be sent a formatted letter to inform them of the
finding. Results will be reviewed at intervals to ensure the study is adequately powered. A
standard statistical package will be used to analyze the results
Progress: This protocol was reported terminated in February 2006, after enrolling only 21 of the
400 subjects required. Study staff cited a lack of interest in continuing the study.
496
Detail Summary Sheet
Date: 30 Sep 06 Number: 206039
Status: Ongoing
Title: SEER Rapid Response Surveillance Study #5, Prostate Cancer Therapy Selection (PCATS)
Study
Principal Investigator: MAJ Karen C. Baker, MC
Department: Surgery/Urology
Facility: MAMC
Associate Investigator(s): MAJ Andrew C. Peterson, MC;
MAJ Keith J. O'Reilly, MC
Start - Completion: Funding:
1/5/2006 - Oct 2006 DCI
Periodic Review:
12/8/2006
Study Objective: The objective of the study is to explore way to improve the treatment
experience for men living with prostate cancer and their families.
Technical Approach: Madigan Army Medical Center will refer patients to Fred Hutchinson
Cancer Research Center for participation in this study. Up to 20 MAMC patients who are not too
distressed will be approached if they meet eligibility criteria and asked to complete a "consent to
contact" form, which will be faxed via confidential line to FHCRC where all other aspects of the
study will be conducted. This is a prospective cohort study of adult men with newly diagnosed
localized prostate cancer, recruited from urology clinics in the SEER regions (Puget Sound Region:
FHCRC, Los Angeles Region: University of Southern California, and the Greater Bay Area Region:
Northern California Cancer Center/Kaiser Permanente). The goal is to enroll a total of 850
subjects; 100 from FHCRC, 150 from USC, and 600 from NCCC/KP. There is no coordinating
center, as each study site is funded independently and will be completing the study independently.
Final data analyses with de-identified data will be pooled and conducted at NCCC/KP.
Progress: This protocol closed to enrollment, with 3 patients enrolled at MAMC. The protocol will
remain ongoing at MAMC pending completion of the study at the other sites.
497
Detail Summary Sheet
Date: 30 Sep 06 Number: 204120 Status: Ongoing
Title: The Effect of Flexible Cystoscopy on the Serum PSA Values
Principal Investigator: MAJ Karen C. Baker, MC
Department: Surgery/Urology Facility: MAMC
Associate Investigator(s): CPT Brian J. DeCastro, MC; MAJ Mark I. Anderson, MC; MAJ
Andrew C. Peterson, MC; CPT Jennifer M. Pugliese, MC; COL Robert C. Allen, MC; MAJ Keith
J. O'Reilly, MC
Start - Completion: Funding: Periodic Review:
2/2/2005 - Nov 2007 DCI 9/26/2006
Study Objective: To determine the affect of flexible cystoscopy on serum PSA values in male
patients with prostates.
Technical Approach: Free and total PSA values will be obtained in 100 males ages 20 to 79
undergoing flexible cystoscopy to evaluate the effect of flexible cystoscopy on serum PSA values.
Because PSA is an important screening test for prostate cancer in men aged 40 through 79, the
number of study participants age less than 40 will be limited to 10 participants each for the age
groups 20 to 29 and 30 to 39. All men will be volunteers who are already scheduled to undergo
flexible cystoscopy. A serum sample for free and total PSA will be drawn up to 1 hour before
flexible cystoscopy and will be the baseline value. Serum samples will be drawn again at 1 hour
after cystoscopy and the day following cystoscopy. If interval analysis after 30 patients shows no
clinically significant difference between the second and third serum samples, the third sample will
be eliminated. The PSA values before and after cystoscopy will be compared with a paired t-test or
the Wilcoxon signed-rank test. Additional variables that could influence the change in PSA values
to include, but not limited to, age, race/ethnicity, prostate size, and reason for cystoscopy will be
recorded and analyzed. Multivariate analysis will be applied once univariate analyses are
completed.
Progress: This protocol closed enrollment after 30 subjects enrolled and an interum analysis
showed statistical signficance but not clinical significance. A manuscript is in progress.
498
Detail Summary Sheet
Date: 30 Sep 06 Number: 205040 Status: Ongoing
Title: The Epidemiology of Nephrolithiasis in Soldiers Returning From Operation Iraqi Freedom
Principal Investigator: MAJ Karen C. Baker, MC
Department: Surgery/Urology Facility: MAMC
Associate Investigator(s): CPT Jennifer M. Pugliese, MC; CPT Brian J. DeCastro, MC; MAJ
Mark I. Anderson, MC; CPT Jack R. Walter, MC; COL Robert C. Allen, MC; MAJ Keith J.
O'Reilly, MC; MAJ Andrew C. Peterson, MC; LTC Maricela Contreras, MC; Charles G. Beleny,
MD
Start - Completion: Funding: Periodic Review:
2/11/2005 - Nov 2008 DCI 1/12/2006
Study Objective: To study the epidemiology of nephrolithiasis in soldiers returning from
Southwestern Asia.
Technical Approach: In this four year descriptive, cohort study a database containing
demographic, military, medical information will be constructed for soldiers returning from
Southwestern Asia who experienced renal colic/nephrolithiasis while deployed. Candidates for the
study will be identified by survey during routine post deployment medical screening at the Soldier
Readiness Point. Soldiers with a history of urinary calculi or renal colic during their deployment
will be referred to the urology clinic evaluation of nephrolithiasis and participation in the
database. A CT scan, appropriate serum chemistries, and screening urine test will be performed on
all subjects. Investigators hope to better describe the epidemiology of stone disease in soldier
deployed in to Southwestern Asia support of Operation Iraqi Freedom and the Global War on
Terrorism.
Progress: This protocol closed to enrollment, with over 6,000 surveys about stone disease collected
from military personnel returning from OIF. Only seven service members with stone disease were
referred to urology and subsequently consented. Data analysis is ongoing.
499
Detail Summary Sheet
Date: 30 Sep 06 Number: 204079 Status: Ongoing
Title: Uniformed Services University National Prostate Cancer Database for the Center for
Prostate Disease Research (CPDR) with Patterns of Care, Outcomes, and Prognostic Analyses,
Protocol Number GT90CM
Principal Investigator: MAJ Karen C. Baker, MC
Department: Surgery/Urology
Facility: MAMC
Associate Investigator(s): MAJ Keith J. O'Reilly, MC
Start - Completion: Funding:
9/22/2004 - Jan 2009 USUHS via Henry M. Jackson Foundation
Periodic Review:
5/10/2006
Study Objective: (1) To collect standardized data on consenting patients treated for prostate
disease at specified centers. (2) To maintain an accurate, reliable, secure relational database of
patients with prostate disease that meets IRB/HIPPA patient safety, private, and confidentiality
guidelines. (3) To coordinate and maintain longitudinal prostate cancer data collection from
various sources as a prostate cancer database repository at USUHS. (4) To analyze patterns of
care, prognostic factors, quality of life and intermediate and long-term outcomes for prostate
cancer and prostate disease entered into this database.
Technical Approach: Subjects previously consented in MAMC #98092 will be rolled over into
this protocol. Subjects will be asked prospectively to enroll in this database if their doctor
recommends that a transrectal ultrasound of the prostate be performed for a medical condition
relating to the prostate. Data will be collected and stored in the CPDR database via stand alone
data entry. This will include information normally collected on newly diagnosed patients with
benign prostatic hypertrophy (BPH) and prostate cancer (CaP) from initial diagnosis to treatment
to follow-up care. The development of the CPDR database simply organizes the information into a
standard format in order to facilitate the data collection process similar to the hospital tumor
registries except that the prostate disease specific information is more comprehensive.
Standardized QOL instruments will be employed prior to treatment and periodically during follow¬
up. The CPDR collaborating statisticians and epidemiologists will be responsible for the quality
assessment of the collected data and for the statistical analysis of future research initiatives. The
electronic data collected by CPDR will reside in the CPDR National Database and maintained on a
secure server at the CPDR Headquarters (part of USUHS) and backed up by the Henry M.
Jackson Foundation. The server maintained at CPDR will contain the National Repository for all
collaborating sites/locations.
A CPDR research file will be maintained on each subject in locked filing cabinets in the Research
Offices of each site. A copy of labs, xrays, bone scans, CT scans, etc., and narrative summaries,
operation report(s) related to prostate cancer treatment, radiation therapy summaries, pathology
report(s), and death certificates if applicable, will be filed on each patient as well as hard copies of
the CPDR forms and the consent form. All sites will use standardized Clinical Research Forms
(CRF) which have been designed and can be used as SF600 encounter forms at each patient visit,
where permitted. The following data collection forms are used to collect data on all prostate
disease patients at participating institutions and are shown and explained in "Forms Manual." (1)
Patient Registration, (2) TRUS biopsy, (3) Pre-treatment Staging, (4) Surgery (Radical
Prostatectomy), (5) Radical Prostatectomy Pathology, (6) Hormonal Therapy, Chemotherapy and
other medications, (7) External Beam Radiation Treatment, (8) Brachytherapy Treatment, (9)
Cryotherapy Treatment, (10) Cryotherapy Follow-up, (11) Follow-up, (12) Update of Medical
History, (13) CPDR Annual Follow-Up Survey, (14) Necropsy
Analysis of Data: The primary purpose of any research database is data analysis to answer
500
research questions and explore hypotheses. With multiple Site Principal Investigators interested
in data analysis, the current system of submitting a CPDR Collaboration consent form will be
used. When the study PI, Site Pi's or other collaborating researchers want to propose an analysis
of multicenter data, a standardized collaboration agreement form will be initiated by the Site PI
and his/her CPDR site Research Data Manager. The site personnel will write the proposal in the
standardized format and forward it to the Regulatory Affairs Office at CPDR Headquarters. After
receiving a CPDR data collaboration request, the Research Opportunity Evaluation Committee at
CPDR HQ will discuss the proposal in terms of data availability, statistical support needed, other
resources required, military relevance, medical significance and publication probability. If the
committee agrees to pursue the proposal and if the request comes from within the CPDR network,
the site is asked to prepare the protocol and submit it according to the site's guidelines, while
CPDR HQ gets the CPDR collaboration consent from all the sites. Upon receipt of the
documentation of approval, CPDR Regulatory Affairs will submit it with a 3204 to USU for
approval. Upon receipt of USU approval, the protocol will be forwarded to all contributing sites to
prepare and submit to their respective IRB's as required. Approvals will be forwarded to USU
REA. If the request comes from outside the CPDR Database network, additional IRB
documentation and other appropriate documents specific to the proposal may be requested. These
will be submitted to REA with the rest of the submission packet for primary review.
Progress: This outcomes database protocol remains open to enrollment, with 69 patients enrolled
at MAMC during FY06, for a total of 1,989 patients enrolled since study approval. The CPDR
continues to perform data collection.
501
Detail Summary Sheet
Date: 30 Sep 06 Number: 202065 Status: Ongoing
Title: Oral Ketoconazole For Prevention Of Postoperative Penile Erection, A Prospective,
Randomized, Double Blind Trial
Principal Investigator: CPT Brian J. DeCastro, MC
Department: Surgery/Urology Facility: MAMC
Associate Investigator(s): MAJ Mark I. Anderson, MC; MAJ Andrew C. Peterson, MC; CPT
Jack R. Walter, MC; MAJ Leah P. McMann, MC; MAJ Karen C. Baker, MC; COL Raymond A.
Costabile, MC; MAJ Keith J. O'Reilly, MC
Start - Completion: Funding: Periodic Review:
5/23/2002 - Dec 2002 DCI 4/25/2006
Study Objective: To determine if Ketoconazole adequately prevents penile erections after penile
surgery.
Technical Approach: This study will be broken into three phases. Phase 1-Patients will be
identified in the urology clinic scheduled to undergo penile or urethral surgery. Prior to surgery,
they will be offered participation and randomized to receive Ketoconazole or placebo. Forty
patients will be randomized in a 1:1 ratio to Ketoconazole or placebo. Phase 2-Forty-eight hours
before surgery, the patient will be started on the study drug (Ketoconazole 400 mg or placebo TID
for a total treatment period of ten days). They will be administered the study questionnaire to fill
out at the end of the treatment period. Phase 3- A follow-up telephone call will be made six weeks
postoperatively to assess patient satisfaction with the outcome of surgery.
Progress: This protocol completed accrual during FY06, with 43 subjects enrolled. Three extra
subjects were required when two subjects withdrew consent without treatment and one subject
had surgery cancelled. The protocol remains ongoing for data analysis of 40 usable data sets.
502
Detail Summary Sheet
Date: 30 Sep 06 Number: 205136 Status: Ongoing
Title: The Incidence of Infection and Stent Colonization in Patients With and Without Strings
Principal Investigator: CPT Brian J. DeCastro, MC
Department: Surgery/Urology Facility: MAMC
Associate Investigator(s): MAJ Steven D. Mahlen, MS; MAJ Keith J. O'Reilly, MC; MAJ
Andrew C. Peterson, MC; MAJ Karen C. Baker, MC; MAJ Mark I. Anderson, MC; CPT Jennifer
M. Pugliese, MC; CPT Dayne M. Nelson, MC; CPT Jennifer L. Gurski, MC
Start - Completion: Funding: Periodic Review:
1/5/2006 - Aug 2007 DCI 8/29/2006
Study Objective: To determine if the presence of an external string attached to an indwelling
ureteral catheter will lead to an increase in the incidence of infection and stent colonization . 2)
To determine which patients are at a higher risk of infection and stent colonization.
Technical Approach: This study is a prospective randomized study looking at the infection rate
of patients with indwelling ureteral stents. Patients will be randomized to two groups. One group
will have nylon strings attached to the stent while the second group will have the strings removed
at the time of surgery. Urine samples and stent cultures will be used to determine if there is a
significant difference in the infection rate of the two groups. Patient demographics will also be
analyzed to see if sex, comorbidities, , duration of stent, or indication for stent placement
contributed to an increased rate of significant infection or stent colonization. Significance will be
determined using the (X2) test with a p value of < 0.05 being significant
Progress: No work was conducted under this protocol due to deployment of study staff.
Enrollment is expected to begin in March 2007.
503
Detail Summary Sheet
Date: 30 Sep 06 Number: 205076 Status: Ongoing
Title: Madigan Army Medical Center's Current Clinical Practice and Experience With
Osteopenia And Fractures In Men Treated With Androgen Deprivation Therapy
Principal Investigator: CPT Dayne M. Nelson, MC
Department: Surgery/Urology Facility: MAMC
Associate Investigator(s): MAJ Keith J. O'Reilly, MC; MAJ Andrew C. Peterson, MC
Start - Completion: Funding: Periodic Review:
5/6/2005 - Mar 2006 DCI 4/20/2006
Study Objective: To determine the incidence of skeletal morbidity and mortality in patients with
prostate cancer receiving androgen deprivation therapy at Madigan, as well as the therapies that
are currently being prescribed.
Technical Approach: This study is a retrospective review of 96 men with prostate cancer
currently receiving Androgen Deprivation Therapy (ADT) in the Urology Clinic, specifically
looking at the incidence and risk of skeletal morbidity and mortality. In addition, an army wide
survey will be conducted with reference to the risks of ADT and the steps army urologists are
taking to prevent and treat skeletal morbidity and mortality. The study will record patient
demographics, number of months of ADT, incidence and types of fractures occurring after
initiation of ADT, results of bone mineral density (BMD) studies conducted after the initiation of
ADT, and the types and frequency of treatment prescribed within our facility. The results of the
army-wide survey will also be recorded. Data will be analyzed to determine the incidence of bone
loss and bone fracture in our patient population currently receiving ADT. The results of the army¬
wide survey will also be analyzed to determine the awareness of the skeletal morbidity and
mortality associated with ADT and what army urologists are doing to monitor, prevent, and treat
these effects.
Progress: This protocol remained ongoing during FY06 to complete final the final manuscript.
504
Detail Summary Sheet
Date: 30 Sep 06 Number: 203053 Status: Completed
Title: A Clinical Trial Evaluating the Safety and Efficacy of ABX-EGF in Patients with Hormone
Resistant Prostate Cancer Elevated PSA With or Without Metastasis, Protocol Number ABX-
0310
Principal Investigator: MAJ Keith J. O'Reilly, MC
Department: Surgery/Urology Facility: MAMC
Associate Investigator(s): COL Robert C. Allen, MC; MAJ Raymond S. Lance, MC; CPT Jack
R. Walter, MC; MAJ Leah P. McMann, MC
Start - Completion: Funding: Periodic Review:
5/9/2003 - May 2005 Abgenix/Immunex via The Geneva Foundation 3/22/2005
Study Objective: Primary objective: To assess the clinical effects determined by the PSA
response of multi-dose administration of 2.5 mg/kg ABX-EGF in HRPC patients with rising PSA
without metastases. Secondary objectives: (a) To examine the pharmacokinetics (PK), (b) to
examine safety profile (including immunogenicity), (c) to assess the overall survival, (d) to evaluate
the time to disease progression, and e) to evaluate the time to PSA progression.
Technical Approach: This study is designed as a multicenter, multiple dose clinical trial to
evaluate the safety and effectiveness of administering ABX-EGF in patients with HRPC.
Approximately 5 patients will be enrolled here at MAMC. Patients will receive 2.5 mg/kg of ABX-
EGF administered IV once a week for 8 weeks per course for a total of 6 treatment courses. The
patient will visit the clinic once a week for 8 weeks. If the patient has had no disease progression
during the initial treatment period they are eligible for the extended treatment period. If the
patient continues with the extended treatment period they will continue to receive 2.5mg/kg of
ABX-EGF for up to 10 months (5 additional 8 week courses of treatment). Patients will be
continually monitored and reassessed for PSA response every 4 weeks. Patients will attend a
safety follow-up visit 4 weeks after their last infusion of ABX-EGF or when the patient is
withdrawn from treatment for any reason. All patients will be followed for assessment of survival
duration for two year following their first infusion of ABX-EGF. During this time patients will be
contacted every three months for survival, status disease status and any cancer
medications/therapies information.
Progress: This protocol closed to enrollment in September 2003, with one patient enrolled at
MAMC who completed treatment and the 24 month survival follow-up via telephone. No internal
serious adverse events were reported. A final site close out visit was conducted in November 2005.
505
Detail Summary Sheet
Date: 30 Sep 06 Number: 205033 Status: Completed
Title: A Phase 2, 8-Week, Multi-Center, Randomized, Double-Blind, Placebo-Controlled, Parallel
Group Study Evaluating the Efficacy, Tolerability and Safety of [S,S]-Reboxetine (PNU-
165442G) for Stress Urinary Incontinence in Women, Protocol A6061023
Principal Investigator: MAJ Keith J. O'Reilly, MC
Department: Surgery/Urology Facility: MAMC
Associate Investigator(s): MAJ Andrew C. Peterson, MC; COL Robert C. Allen, MC; MAJ
Karen C. Baker, MC; CPT Brian J. DeCastro, MC
Start - Completion: Funding: Periodic Review:
4/20/2005 - Jan 2006 Pfizer via The Geneva Foundation 1/18/2006
Study Objective: Proof of concept study to assess the efficacy, tolerability and safety of SS-RBX
vs. placebo in the treatment of SUI and to evaluate whether an upward dose adjustment affects
the tolerability of SS-RBX.
Technical Approach: This is a randomized, double-blind, placebo controlled, 4-treatment arms
(placebo and 3 active) comprised of 4 phases: (1) Drug free run-in period of 2 weeks, (2) Single
blind placebo run-in period of 2 weeks. (3) 8 weeks double blind randomized treatment period and
(4) 2 week follow up period. Those subjects entering the 8 week treatment phase will be
randomized into the following groups in a 1:1:1:3 ratio: (1) Group 1 SS-RBX 2mg QD, increasing to
SS-RBX 4mg QD after 4 weeks, (2) Group 2 SS-RBX4mg QD for eight weeks, (3) Group 3 SS-RBX
4mg QD, increasing to SS-RBX 6mg QD after 4 weeks and (4) Group 4 Placebo. A follow up visit
will occur 2 weeks after the treatment period has been completed. Subjects will not be able to
down-titrate their dose. Subjects unable to tolerate study drug will have to be withdrawn from the
study. It is expected that approximately 600-800 subjects will be screened in order to randomize
400 subjects. Approximately 40-60 sites will be recruiting into the study. Subjects will undergo
stratification at randomization using incontinence episode frequency (Group A <14 episodes/week;
Group B > 14 episodes/week. This will be calculated from the self-reported diary data collected just
prior to V4 (week 0).
Progress: This protocol closed to enrollment 13 February 2006, with no subjects screened or
enrolled at MAMC.
506
Detail Summary Sheet
Date: 30 Sep 06 Number: 206024 Status: Terminated
Title: A Twelve-Week Randomized, Double-Blind, Placebo-Controlled, Parallel Group, Forced
Titration, Proof of Concept Study to Assess the Efficacy, Safety and Tolerability as well as the
Pharmacokinetic Profile of 60 mg and 120 mg of GW679769 (GW679769) administered once daily
vs. Placebo in Women with Overactive Bladder
Principal Investigator: MAJ Keith J. O'Reilly, MC
Department: Surgery/Urology Facility: MAMC
Associate Investigator(s): MAJ Karen C. Baker, MC; MAJ Andrew C. Peterson, MC
Start - Completion: Funding: Periodic Review:
2/28/2006 - Nov 2006 GlaxoSmithKline via The Geneva Foundation N/A
Study Objective: The primary objective is to compare the efficacy of GW679769 administered
once daily for 12 weeks (60 mg for 6 weeks, followed by 120 mg for 6 weeks) and placebo in female
subjects with overactive bladder (symptoms of urgency with urge incontinence and frequency
which may be associated with nocturia).
Secondary objectives are to evaluate the safety and tolerability of GW679769 administered once
daily for 12 weeks (60 mg for 6 weeks, followed by 120 mg for 6 weeks) compared to that of placebo
in female subjects with overactive bladder (symptoms of urgency with urge incontinence and
frequency which may be associated with nocturia); to describe the exposure of both GW679769 and
its primary metabolite (GSK525060) after 12 weeks of dosing (60 mg for 6 weeks, followed by 120
mg for 6 weeks) in female subjects with overactive bladder; and to explore the relationship of
GW679769 and its primary metabolite (GSK525060) with clinical response/safety after 12 weeks of
dosing (60 mg for 6 weeks, followed by 120 mg for 6 weeks) in female subjects with overactive
bladder.
Technical Approach: This is a phase Ha, multi-center, randomized, double-blind, forced
titration, placebo-controlled, parallel group study of GW679769 in female subjects 18 years of age
but not older than 65 with OAB with symptoms of urgency with urge incontinence and frequency
which may be associated with nocturia but without bladder related pain. The study will consist of
a 1 or 2 week treatment-free run-in period followed by a 12 week treatment period. After
completion of the treatment period, subjects will return approximately one week later for their
follow-up visit.
During the one or two week treatment-free run-in period, subjects will be restricted from taking
any medications used to treat OAB and maintain an electronic diary beginning 3 days immediately
prior to the randomization visit. If subjects meet the inclusion criteria, they will be randomized
into the 12-week, double-blind treatment phase and receive either GW679769 (60 mg and 120 mg)
or placebo. After 2 weeks of evening dosing, subjects will begin to take their study medication in
the morning (AM) and continue with this dosing regimen throughout the remainder of the study.
After 6 weeks of treatment, all subjects initially randomized to 60 mg of GW679769 will be titrated
to the higher dose of 120 mg of GW679769 and remain on this treatment for an additional 6 weeks.
Subjects randomized to placebo will remain on placebo for the entire 12 weeks of treatment. Safety
and tolerability of the assigned treatment will also be assessed. All subjects will participate in the
population PK analysis where a total of 6 samples per subject will be taken for analysis during the
course of the study. Approximately 1 week after completion of the Treatment Period, subjects will
return for a follow-up visit.
507
Progress: The study sponsor terminated MAMC as a study site 24 April 2006, with no patients
enrolled. The screening of MAMC patients was planned for July 2006, and the study was expected
to close to enrollment at that time.
508
Detail Summary Sheet
Date: 30 Sep 06 Number: 204116 Status: Completed
Title: Phase 2, Multi-Center, Randomized, Double-blind, Placebo-Controlled, 3 Arm, 12-Month
Study to Evaluate the Effects of GPI 1485 on Erectile Function in Patients Undergoing Bilateral
Nerve-Sparing Radical Retropubic Prostatectomy for Prostatic Carcinoma, Protocol Number
0501-0202
Principal Investigator: MAJ Keith J. O'Reilly, MC
Department: Surgery/Urology Facility: MAMC
Associate Investigator(s): MAJ Andrew C. Peterson, MC; MAJ Karen C. Baker, MC; COL
Robert C. Allen, MC; OPT Brian J. DeCastro, MC; CPT Jack R. Walter, MC; Tammie Bousquet-
Cordes, LPN
Start - Completion: Funding: Periodic Review:
11/5/2004 - Aug 2005 Guilford Pharmaceuticals Inc. via The Geneva 8/23/2005
Foundation
Study Objective: Primary objectives: (1) To compare the effect of a 6-month course of GPI 1485
1000 mg QID vs. a 6-month course of placebo on the EF domain of the IIEF questionnaire 6
months post-NSRRP in men 40-59 years of age. (2) To compare the effect of a 6-month course of
GPI 1485 400 mg QID vs. a 6-month course of placebo on the EF domain of the IIEF questionnaire
6 months post-NSRRP in men 40-59 years of age. Secondary objectives: (1) To compare the effect of
a 6-month course of GPI 1485 1000 mg QID vs. a 6-month course of placebo on the EF domain of
the IIEF questionnaire 6 months post-NSRRP in men 60-69 years of age. (2) To compare the effect
of a 6-month course of GPI 1485 400 mg QID vs. a 6-month course of placebo on the EF domain of
the IIEF questionnaire 6 months post-NSRRP in men 60-69 years of age. (3) To compare in each
age group the effect of GPI 1485 vs. placebo on the EF domain of the IIEF questionnaire 3, 9, and
12 months post-NSRRP. (4) To compare in each age group the time to first recovery of EF curve in
each of the GPI 1485 treated group vs. the placebo treated group using a score of 26 on the EF
domain of the IIEF questionnaire. (5) To compare in each age group the effects of the 2 active GPI
1485 treatment groups on the EF domain of the IIEF questionnaire. (6) To compare in each age
group Viagra® use over an 11-month period in the GPI 1485 vs. placebo treated groups. (7) To
examine in each age group Health Related Quality of Life (HRQOL) status post-NSRRP using the
RAND 12-item Health Survey v2 (SF-12 v2) and the UCLA Prostate Cancer Index Short Form. (8)
To evaluate in each age group the safety of GPI 1485. (9) To evaluate in each age group the
pharmacokinetics of GPI 1485. (10) To evaluate the efficacy and safety for age-combined GPI 1485
and placebo groups.
Technical Approach: This trial will be multi-center, randomized, double-blind, placebo-
controlled, 3-arm study to evaluate in men 40-59 years of age the effects of GPI 1485, 1000 mg QID
and GPI 1485, 400 mg QID on erectile function post-Bilateral Nerve Sparing Retropubic Radical
Prostatectomy (NSRRP) after 6 months of treatment. During an additional 6 months of follow-up,
the study will evaluate long-term benefits of GPI 1485. Randomization will be stratified by age
group (40-59 vs. 60-69 years of age) and by site. Patients will be randomized to one of three study
arms in a 1:1:1 ratio. Arm 1: GPI 1485 1000 mg QID for 6 months; Arm 2: GPI 1485 400 mg QID
for 6 months; Arm 3: Placebo QID for 6 months. Patients meeting screening criteria and enroll in
the study will have a total of 8 protocol specified visits for safety, concomitant medication, and
compliance assessments. Six will be office visits: screening visit, baseline visit (Visit 0), surgical
period (Visit 1), and visits after approximately 3 (Visit 3), 6 (Visit 4), and 12 (Visit 6) months post¬
surgery. There will also be two telephone follow-up visits after approximately 1 month (Visit 2)
and 9 (Visit 5) months post-surgery. Patients will also have electronic Patient Experience Diary
efficacy visits at 3, 4, 5, 6, 7, 8, 9, 10, 11, and 12 months post-surgery. Patients will not be required
to return to the office or speak to study personnel over the telephone in order to complete the
509
electronic PED visits, but will be required to complete protocol specified study questionnaires via
an electronic PED. The electronic PED will be used daily to track randomized study medication
use until 6 months post-surgery. The electronic PED will be used weekly to track Viagra® use
from 1 to 12 months post-surgery.
Progress: This protocol closed to enrollment in March 2005, and a site close out visit conducted in
May 2006, by phone. Two subjects were randomized, one completed study treatment, and one
withdrew consent. No internal serious adverse events were reported.
510
Detail Summary Sheet
Date: 30 Sep 06 Number: 205073 Status: Ongoing
Title: A Phase 2, Randomized, Multicenter, Placebo-Controlled, Double-Blind Dose-Ranging
Clinical Trial to Study the Efficacy and Safety of 5, 15, or 25 mg/day of CyPat™ (Cyproterone
Acetate) for the Treatment of Hot Flashes following Surgical or Medical Castration of Prostate
Cancer Patients, Protocol #DR-PCA-201
Principal Investigator: MAJ Andrew C. Peterson, MC
Department: Surgery/Urology Facility: MAMC
Associate Investigator(s): MAJ Karen C. Baker, MC; ; Dieter Kirchheim, MD; MAJ Michael J.
Sebesta, MC; CPT Jennifer M. Pugliese, MC; CPT Brian J. DeCastro, MC; COL Robert C. Allen,
MC; MAJ Keith J. O'Reilly, MC
Start - Completion: Funding: Periodic Review:
7/26/2005 - Jun 2006 Duramed via The Geneva Foundation 4/25/2006
Study Objective: Primary objectives are to compare the efficacy of 5, 15 and 25 mg/day of
CyPat™ to placebo when used as "add-on" therapy in reducing the frequency and average severity
of moderate to severe hot flashes; to compare the safety of 5, 15 an 25 mg/day CyPat™ to placebo
when used as "add-on" therapy; based on the efficacy and safety of each dose, identify the
minimally effective dose to be evaluated in a future Phase 3 study. Secondary objectives are to
compare the efficacy of 5, 15 and 25 mg/day of CyPat™ to placebo when used as "add-on" therapy
in reducing the average severity of all hot flashes and to compare the efficacy of 5, 15 and 25
mg/day of CyPat™ to placebo when used as "add-on" therapy in elimination of all hot flashes.
Technical Approach: Randomized, double-blind, placebo-controlled 12-week study to compare
the efficacy and safety of 5, 15 and 25 mg/day CyPat™ to placebo when used as "add-on" therapy
in addition to a stable course of standard pharmacological therapy for prostate cancer in patients
with mild to moderate vasomotor symptoms (hot flashes) following surgical or medical castration.
A total of 400 patients will be randomized, 100 per treatment arm to achieve 75 analyzable
patients per arm. After consenting on the first day of Screening Period, potential patients will have
the following: medical history-including history of hot flashes, physical examination-including
assessment of known thromboembolic risk factors, and clinical laboratory evaluations. Once
results of the Screening Period evaluations are obtained, those patients thought to be likely to
meet the inclusion and none of the exclusion criteria will be invited to participate in a one week
single-blind placebo run-in period. Patients must demonstrate at least 21 moderate to severe hot
flashes during the 7-day Placebo Run-In Period (this number may be prorated based on the actual
duration of the run-in period). Four hundred patients found to meet all the eligibility criteria
following the single-blind Placebo Run-In Period will be randomized equally to one of the four
double-blind treatment groups: CyPat™ 5, 15 or 25 mg/day or to placebo for a total of 12 weeks.
Patients will return for follow-up evaluations each month after beginning double-blind treatment.
Patients will maintain a daily paper diary to record the frequency and severity of hot flashes
during the treatment period. In addition, a brief physical evaluation will be done, diaries will be
reviewed and any adverse events will be recorded at each follow-up evaluation.
Progress: This protocol remains open to enrollment with one patient who screen failed due to a
lack of hot flashes.
511
Detail Summary Sheet
Date: 30 Sep 06 Number: 205086 Status: Completed
Title: A Randomized, Double Blind, Placebo and Active-Controlled Efficacy and Safety Study of
SSR240600C, in Patients with Overactive Bladder or Urge Urinary Incontinence, Protocol # ACT
5190
Principal Investigator: MAJ Andrew C. Peterson, MC
Department: Surgery/Urology Facility: MAMC
Associate Investigator(s): COL Robert C. Allen, MC; MAJ Keith J. O'Reilly, MC; MAJ Karen
C. Baker, MC
Start - Completion: Funding: Periodic Review:
9/1/2005 - May 2006 Sanofi Aventis via The Geneva Foundation 8/10/2006
Study Objective: Primary objective is to evaluate the effect of SSR240600C versus placebo, on
maximum bladder capacity using cystometry in Over active Bladder (OAB), Urge Urinary
Incontinence (UUI) patients. Secondary objectives will be to assess the effect of SSR240600C on:
(1) Additional cystometric endpoints including: maximum detrusor pressure, volume at first desire
to void, volume at first unstable contraction. (2) Clinical Endpoints including: micturition
frequency, .incontinence episodes, urgency episodes, nocturia (each per 24 hours), and subjective
measures including patient's perception of improvement and quality of life measures and (3)
Safety and tolerability including adverse event assessment, laboratory and ECG monitoring.
Technical Approach: This is a multicenter, prospective, randomized, double blind, and placebo
controlled study with calibrator. Patients will be randomly assigned to one of three groups: (1)
SSR240600C 500mg/day (2) Tolterodine 4 mg/day, (3) Matching Placebo. Subjects will be selected
based on clinical signs and symptoms and urodynamic confirmation consistent with a diagnosis of
OAB/UUI. Following initial screening and obtaining informed consent, the subject will be
instructed on the completion of a voiding diary. If eligible according to the inclusion/exclusion
criteria the subject will be randomized to one of the groups noted above and treated for 4 weeks.
Cystometrograms (CMG) will be performed at randomization visit prior to study drug intake, and
at the completion of four weeks of treatment. In addition to the cystometric endpoints, additional
therapeutic efficacy parameters will be recorded through the use of daily voiding diaries, a health
related quality of life measure (King's Health Questionnaire) and a subjective assessment of
disease state (Visual Analog Scale). The study will consist of a 7-day screening period followed by a
four-week treatment period, completing a 7-day follow-up period, for total patient participation
duration of approximately 42 days.
Progress: A study site close out visit was conducted in August 2006; no subjects were enrolled in
this protocol and no outstanding regulatory issues were reported.
512
Detail Summary Sheet
Date: 30 Sep 06 Number: 205116 Status: Terminated
Title: A Randomized, Double-Blind, Parallel-Design, Placebo Controlled Study to Evaluate the
Effects of 5 mg Tadalafil (IC351, LY450190) and 50 mg Sildenafil Administered Once Daily for 6
Months on Visual Function in Healthy Subjects or Subjects with Mild Erectile Dysfunction,
Protocol H6D-MC-LVGO
Principal Investigator: MAJ Andrew C. Peterson, MC
Department: Surgery/Urology Facility: MAMC
Associate Investigator(s): MAJ Karen C. Baker, MC; COL Robert C. Allen, MC; LTC William
R. Raymond IV, MC; LTC Roger K. George, MC; COL Elizabeth A. Hansen, MC; COL Robert A.
Mazzoli, MC; LTC Darryl J. Ainbinder, MC; COL Craig D. Hartranft, MC; LTC Mark L. Nelson,
MC; MAJ Keith J. O'Reilly, MC
Start - Completion: Funding: Periodic Review:
11/4/2005 - Jul 2006 Lilly ICOS LLC via The Geneva Foundation 8/10/2006
Study Objective: The primary objective of the trial is to evaluate mean changes from baseline to
endpoint in dark-adapted bright flash b-wave amplitude on ERG in healthy subjects or subjects
with mild ED receiving daily administration of 5 mg tadalafil compared to subjects receiving
placebo for 6 months. Secondary objectives (1) the effects of daily administration of 5 mg tadalafil
compared with placebo after 3 and 6 months, (2) the effects of daily administration of 50 mg
sildenafil compared with placebo after 3 and 6 months, (3) the reversibility of any visual effects
(should they be observed) 4 to 6 weeks after 6 months of daily dosing.
Technical Approach: This is a multicenter, randomized, double-blind, placebo-controlled,
parallel-design study to evaluate the effects on vision of daily dosing of 5 mg Tadalafil or 50 mg
Sildenafil compared with placebo. Approximately 198 subjects (approximately 66 subjects per
treatment group) will be randomized in this study. Stratified randomization will be used to ensure
a 1:1:1 ratio of 5 mg tadalafil to 50 mg sildenafil to placebo with regard to the following factors:
Base OU (both eyes) average dark-adapted bright flash b-wave amplitude (<400 V, >400 V),
investigator site, and subject age (<50, >50 years).
The study consists of 3 periods, Screening Period, Daily Treatment Period, and a Washout Period:
During the one month screening period (Visits 1-2), subjects will be consented and evaluated to see
if they meet the inclusion and exclusion criterion and then undergo the first of two ophthalmology
exams, which will consist of visual acuity testing with refraction, intraocular pressure
measurement, Farnsworth-Munsell (FM100) hue test, peripheral vision measurement, retinal
inspection, anterior chamber inspection, and lens/cataract grading. These screening tests will
serve as baseline measurements for statistical analyses.
The Daily treatment period will last approximately 6 months (Visit 3-5). At visit 3, the subject will
undergo ERG testing, which will serve as a baseline ERG for statistical analyses. If subjects do not
exhibit any ERG parameters outside the age-adjusted normative range for that study site, they are
eligible for randomization and will receive study drug and be instructed to take one capsule daily
beginning the following day. On the days of visits 4 and 5, subjects will omit their dose of study
drug for those days and report to the research site with the package of study drug dispensed at the
previous visit. The subject will receive a dose of study drug from the returned package and then
undergo a complete ophthalmology exam. This exam will be timed so that the ERG testing
approximately coincides with peak plasma levels for the drugs Tadalafil and Sildenafil. Should
abnormalities on visual testing be observed at visit 4, the PI may bring the subject back for further
evaluation and retesting within approximately 2 weeks.
513
After visit 5, subjects will discontinue study drug, enter a 4-6 week washout period and return for
Visit 6 (post -treatment follow-up). At visit 6, subjects will undergo a completed ophthalmology
exam. Subjects will not receive a dose of study drug at this time. The purpose of this post¬
treatment follow-up is to evaluate the reversibility of any abnormality identified during testing at
visits 4 or 5. The study is complete after visit 6.
Progress: This protocol closed to enrollment in February 2006, with no subjects enrolled at
MAMC. CIRO terminated this protocol 14 August 2006, due to an unusually long wait for the
study sponsor to conduct a site close out visit.
514
Detail Summary Sheet
Date: 30 Sep 06 Number: 205027 Status: Ongoing
Title: A Randomized, Double-Blind, Placebo-Controlled, Multicenter Efficacy and Safety Study
of Toremifene Citrate for the Prevention of Prostate Cancer in Men with High Grade Prostatic
Intraepithelial Neoplasia (PIN)
Principal Investigator: MAJ Andrew C. Peterson, MC
Department: Surgery/Urology Facility: MAMC
Associate Investigator(s): MAJ Karen C. Baker, MC; ; MAJ Michael J. Sebesta, MC; CPT
Jennifer M. Pugliese, MC; Dieter Kirchheim, MD; COL Robert C. Allen, MC; MAJ Keith J.
O'Reilly, MC
Start - Completion: Funding: Periodic Review:
3/22/2005 - Feb 2007 GTx, Inc. via Geneva 12/13/2005
Study Objective: The primary objective of this study is to assess the efficacy of toremifene in the
prevention of prostate cancer in men with high grade prostatic intraepithelial neoplasia (PIN). The
Secondary objectives of this study are: (1) To assess the safety of toremifene in men with high
grade PIN, (2) To assess the effect of toremifene in high grade PIN, (3) To assess the effect of
toremifene on lipid levels, (4) To assess the effect of toremifene on hormone levels, (5) To assess the
effect of toremifene on total and % free serum PSA levels, (6) To assess the effect of toremifene on
AUA symptom score.
Technical Approach: There will be two treatment groups included in this trial. One treatment
group will receive tablets containing 20 mg toremifene to be taken daily. The other treatment
group will receive matching placebo tablets to be taken daily. Each subject randomized into this
study will receive up to 36 months of treatment with a tablet containing 20 mg toremifene or
matching placebo tablets. The Screening evaluation includes procedures that are necessary to
determine subject eligibility for study treatment. The baseline evaluation is defined as an
assessment of subject status prior to any study treatment. If the subject is randomized into this
study, the results obtained during the screening and/or randomization visits may be used for the
baseline evaluation and comparison with results obtained during or at the completion of the study.
Patients will have a 3, 6, 12, 18, 24, 30, and 36 month visits. The primary endpoint will be the
diagnosis of prostate cancer through prostate biopsy at 12, 24 or 37 months.
Progress: This protocol closed to enrollment with eight patients screened at MAMC. Three
patients are actively enrolled and remain on study treatment. Three screen-failed and two patients
withdrew consent.
515
Detail Summary Sheet
Date: 30 Sep 06 Number: 203042 Status: Ongoing
Title: A Randomized, Double-Blind, Placebo-Controlled, Parallel Group Study of the Efficacy
and Safety of Dutasteride 0.5 mg Administered Orally Once Daily for Four Years to Reduce the
Risk of Biopsy- Detectable Prostate Cancer, Protocol Number ARI40006
Principal Investigator: MAJ Andrew C. Peterson, MC
Department: Surgery/Urology Facility: MAMC
Associate Investigator(s): MAJ Karen C. Baker, MC; ; MAJ Michael J. Sebesta, MC; CPT
Jennifer M. Pugliese, MC; COL Robert C. Allen, MC; MAJ Keith J. O'Reilly, MC
Start - Completion: Funding: Periodic Review:
5/6/2003 - Mar 2007 GlaxoSmithKline via The Geneva Foundation 1/24/2006
Study Objective: The primary objective of this study is to assess the effect of repeat oral once
daily dosing of 0,5mg Dutasteride compared to placebo on the risk of biopsy-detectable carcinoma
of the prostate after 2 years and 4 years of treatment.
Technical Approach: This is a four-year, international, multicenter, randomized, double-blind,
placebo-controlled parallel group study to evaluate the efficacy and safety of oral, once daily dosing
0.5mg of Dutasteride in reducing the risk of biopsy detectable prostate cancer in men with
suspicious PSA and an initial negative prostate biopsy who are thereby at increased risk for
developing prostate cancer. Approximately 18 patients will be enrolled here at MAMC. Patients
will complete a 4 week placebo run-in followed by randomization to either 0.5 mg Dutasteride or
placebo in a 1:1 ratio. For up to 4 years, patients will be given a 6 month supply of study
medication to self administer. Patients will return to the clinic every 6 months for assessments
and a re- supply of medication until study termination. Patients will be contacted by phone 3
months after each clinic visit and 4 months after the final dose of study medication to assess
adverse events and concomitant medications. All patients will undergo a TRUS at 2 years and 4
years.
Progress: A total of 16 patients enrolled in this study at MAMC. Seven patients were screen
failures and 9 were randomized and remain on study treatment. This study is closed to new
enrollment; however, previously enrolled patients will continue in the study for the duration of 2
years.
516
Detail Summary Sheet
Date: 30 Sep 06 Number: 205135 Status: Ongoing
Title: Acute Urinary Retention and the Role of Fill and Pull Voiding Trials
Principal Investigator: MAJ Andrew C. Peterson, MC
Department: Surgery/Urology Facility: MAMC
Associate Investigator(s): CPT Brian J. DeCastro, MC; CPT Jennifer M. Pugliese, MC; COL
Robert C. Allen, MC; MAJ Keith J. O'Reilly, MC; MAJ Karen C. Baker, MC; MAJ Mark I.
Anderson, MC; CPT Dayne M. Nelson, MC
Start - Completion: Funding: Periodic Review:
1/5/2006 - Sep 2007 DCI 8/29/2006
Study Objective: Define the role of fill and pull voiding trials versus simple catheter removal in
men with acute urinary retention.
Technical Approach: This is a prospective randomized study of 100 patients who present to the
Urology clinic with acute urinary retention. These patients have or will have a Foley catheter
placed to drain their bladder on presentation. Initial evaluation will include urinalysis, urine
culture, and routine serum studies. Patients will be started on tamsulosin if not contraindicated
or already on alpha-blocker therapy. Those already on alpha-blockers will continue the original
therapy. Patients will follow-up with the urology service for catheter removal on day 5-7.
Patients will have complete history and physical examination and be randomized to fill and pull
voiding trial or catheter removal following consent. Fifty patients will be included in each arm of
the study. Patients will have a transrectal ultrasound to size prostate at time of catheter removal.
If patients pass voiding trial they will have a follow-up visit at 1 month to assess voiding
symptoms. If patients fail voiding trial they will continue with catheter drainage for an additional
5-7 days and have the same method of catheter removal. If patients have success they will have
the above follow-up. If patients fail the voiding trial for a second time, they will undergo
urodynamics and be managed by current standards of care. Data recorded will include; the cause
of retention, American Urologic Association symptom and bother score, serum creatinine, prostate
serum antigen (PSA), urine analysis and culture results, prostate size, outcome of voiding trial,
and 3 month follow up data.
Progress: No work was conducted under this protocol in FY06, due to deployment of study staff. A
change of PI from CPT DeCastro to MAJ Peterson was approved; enrollment is planned to being in
October 2006, with the assistance of the new AI, Dr. Pugliese.
517
Detail Summary Sheet
Date: 30 Sep 06 Number: 206031 Status: Ongoing
Title: Adult Circumcision: Template vs Standard Sleeve Technique
Principal Investigator: MAJ Andrew C. Peterson, MC
Department: Surgery/Urology Facility: MAMC
Associate Investigator(s): CPT Brian J. DeCastro, MC; MAJ Karen C. Baker, MC; MAJ Mark
I. Anderson, MC; CPT Jennifer M. Pugliese, MC; CPT Dayne M. Nelson, MC
Start - Completion: Funding: Periodic Review:
2/22/2006 - Jan 2008 DCI 12/12/2006
Study Objective: To compare the Adult template circumcision with the standard sleeve
technique.
Technical Approach: This study is a prospective randomized study comparing the standard
sleeve technique (current standard) with the Adult template circumcision technique. Patients will
be randomized to two groups containing 50 patients each. An interim analysis will be done at 50
patients. The two groups will be compared by operative times, blood loss, complication rates, and
overall patient satisfaction as assessed by the attached patient satisfaction form. Significance will
be determined using the (X2) test with a p value of < 0.05 being significant.
Progress: This protocol remains open to patient entry, with no subjects enrolled to date.
518
Detail Summary Sheet
Date: 30 Sep 06 Number: 206117 Status: Ongoing
Title: Comparison of Non-Contrast Abdominal Computed Tomography (CT) to Contrast CT,
Intravenous Pyelography (IVP) and Nuclear Renal Scan for Determination of Renal Function: A
Retrospective Review
Principal Investigator: MAJ Andrew C. Peterson, MC
Department: Surgery/Urology
Facility: MAMC
Associate Investigator(s): CPT Jennifer L. Gurski, MC
Start - Completion:
Funding:
Periodic Review:
8/15/2006 - Sep 2006
DCI
N/A
Study Objective: Objective is to establish the ability of non-contrast CT ("stone protocol CT") to
determine renal function without the use of intravenous contrast or radio-pharmaceutical (IVP,
contrast CT, or nuclear renal scan).
Technical Approach: The CHCS database will be reviewed for patients who have undergone
non-contrast CT scanning of the abdomen for any diagnosis. Patients who have undergone
subsequent functional studies in addition to the non-contrast study will be included in the study.
A multivariate analysis will be performed to determine if non-contrast CT scanning can be used to
estimate renal function without the use of contrast agents or radio-pharmaceuticals.
Progress: This minimal risk protocol received initial approval by the Expedited Review
Committee, effective 15 August 2006. Initiation is pending a list of patients from the Department
of Radiology.
519
Detail Summary Sheet
Date: 30 Sep 06 Number: 202122 Status: Ongoing
Title: Followup of Testicular Microlithiasis in an Asymptomatic Population
Principal Investigator: MAJ Andrew C. Peterson, MC
Department: Surgery/Urology Facility: MAMC
Associate Investigator(s): MAJ Mark I. Anderson, MC; CPT Brian J. DeCastro, MC; CPT
Jennifer M. Pugliese, MC; MAJ Leah P. McMann, MC; CPT Frederick L. Stephens II, MC; COL
Raymond A. Costabile, MC
Start - Completion: Funding: Periodic Review:
12/27/0253 - Dec 2002 DCI 6/8/2006
Study Objective: To determine the incidence of testis tumor at two, five, and ten-year follow-up
in the 84 men previously identified with testicular microlithiasis in the original study by Peterson
et al. entitled The Prevalence Of Testicular Microlithiasis in an Asymptomatic Screening
Population.
Technical Approach: Patients will be identified through the data collected at ROTC Advance
Camp 2000. All patients identified with TM will be contacted by telephone. If they agree to
participate, the study investigator will administer a telephonic questionnaire on year 2002, 2005,
and 2010.
Progress: This protocol remains ongoing for continued follow-up for the possible development of
cancer in a high risk group of 63 subjects that enrolled. Subjects have been contacted by phone, e-
mail, and mail. One participant has developed testicle cancer since last follow up.
520
Detail Summary Sheet
Date: 30 Sep 06 Number: 204078 Status: Ongoing
Title: Long-Term Open-Label Extension Trial for Subjects Completing the Phase 3 Trial of
Fesoterodine (SP584) for the Treatment of Overactive Bladder Syndrome
Principal Investigator: MAJ Andrew C. Peterson, MC
Department: Surgery/Urology Facility: MAMC
Associate Investigator(s): MAJ Karen C. Baker, MC; ; MAJ Michael J. Sebesta, MC; CPT
Jennifer M. Pugliese, MC; MAJ Keith J. O'Reilly, MC; COL Robert C. Allen, MC; MAJ Leah P.
McMann, MC
Start - Completion: Funding: Periodic Review:
8/24/2004 - Apr 2005 Schwarz Biosciences via The Geneva 5/23/2006
Foundation
Study Objective: Long-term data on safety, satisfaction and maintenance in subjects taking
fesoterodine will be obtained. The subject satisfaction and the treatment benefit of fesoterodine
will be assessed.
Technical Approach: SP739 is the open-label extension of the double-blind phase 3 trial SP584.
Subjects completing the 12 week treatment period in SP584 will have the opportunity to
participate in this extension trial. Subjects will be treated from the time of enrollment until
fesoterodine becomes commercially available, but no longer than 3 years after enrollment. All
subjects will receive 8 mg fesoterodine hydrogen fumarate at the start of the trial. Each subject
may request a one time dose reduction to 4 mg fesoterodine hydrogen fumarate after the subject
has been on 8 mg fesoterodine hydrogen fumarate for at least 1 month, during a scheduled site
visit and upon discussion with the investigator. Such subjects will also be permitted to increase
back to 8 mg fesoterodine hydrogen fumarate. This decision can only be made during a scheduled
site visit and upon discussion with the investigator. This process can be followed on an annual
basis. At a maximum, the number of subjects for this trial will be 810. However, since it is likely
that not all subjects treated in SP584 will qualify and choose to enter the long-term open-label
extension, it is estimated that at least 450 subjects will be enrolled in SP739.
Progress: This protocol closed to enrollment with five patients enrolled at MAMC. One patient
completed the study, two patients withdrew consent and one patient remaind on active study
medication during FY06.
521
Detail Summary Sheet
Date: 30 Sep 06 Number: 206102 Status: Ongoing
Title: Phase II, multicentre, randomised, double-blind, placebo-controlled, pilot study to
determine proof of efficacy, safety, tolerability and pharmacokinetics of intravesical PSD597 in
the symptomatic management of interstitial cystitis/painful bladder syndrome (I C/PBS)
Principal Investigator: MAJ Andrew C. Peterson, MC
Department: Surgery/Urology
Facility: MAMC
Associate Investigator(s): CPT Jennifer M. Pugliese, MC
Start - Completion: Funding:
9/13/2006 - Dec 2006 Geneva via The Geneva Foundation
Periodic Review:
N/A
Study Objective: Primary Objective: To assess the percentage of patients who respond to
PSD597, assessed as "moderately improved" or "markedly improved" measured by a Global
Response Assessment (GRA), compared to placebo, at day 15 following a 5-consecutive day course
of treatment.
Secondary Objectives: (1) To assess changes in GRA measured by a 7-point scale, (2) to assess
changes in bladder pain measured by 10-point Likert scale, (3) to assess changes in frequency
measured by a voiding log, (4) to assess changes in urgency measured by 10-point Likert scale, (5)
to assess changes in symptoms and problems associated with interstitial cystitis measured by the
O'Leary Sant Interstitial Cystitis symptom and problem indexes (6) to assess the safety and
tolerability of PSD597 instilled into the bladder and (7) to characterize the pharmacokinetics of
single and multiple doses of intravesical PSD597 in a sub-group of patients.
Technical Approach: This is a phase II, multicenter, randomized, double-blind, placebo-
controlled, parallel group, pilot study to determine proof of efficacy, safety, tolerability and
pharmacokinetics of intravesical PSD597 in the symptomatic management of IC/PBS. 100 subjects
with a clinical diagnosis of IC/PBS with symptoms persisting for at least three months prior to
study entry and including pain of bladder origin will be enrolled into the study. Following consent,
subjects will undergo screening procedures in the clinic within 14 days prior to baseline (day 1). At
baseline (day 1), all eligible subjects will be randomly allocated (1:1) to treatment with PSD597 or
placebo. Double-blind treatment will be given as a daily instillation for five consecutive days
(Monday - Friday, days 1 - 5), to be administered in hospital as an outpatient. Following double¬
blind treatment, all subjects will attend clinic for follow-up evaluations on days 8 and 15. All
subjects will then be offered the option of open-label treatment with PSD597 for five further days
(Monday - Friday, days 15 - 19) - administered in hospital as an outpatient. All subjects, whether
or not they opt to receive open-label treatment, will attend clinic for further final follow-up
evaluations on days 22 and 29.
Progress: This protocol remains open to patient entry, with no patients enrolled.
522
Detail Summary Sheet
Date: 30 Sep 06 Number: 204032 Status: Ongoing
Title: Prospective, Observational Registry and Patient Survey of the Management of Men with
Symptomatic Benign Prostatic Hyperplasia (BPH): BPH Registry and Patient Survey Protocol
#L8890
Principal Investigator: MAJ Andrew C. Peterson, MC
Department: Surgery/Urology
Facility: MAMC
Associate Investigator(s): MAJ Karen C. Baker, MC; COL Robert C. Allen, MC; MAJ Keith J.
O'Reilly, MC
Start - Completion: Funding:
4/5/2004 - Jan 2005 Sanofi-Synthelabo, Inc. via The Geneva
Foundation
Periodic Review:
1/18/2006
Study Objective: The aim of the overall registry is to examine the characteristics, management
practices, and patient outcomes, including symptom amelioration and disease progression, while
exploring the effects of demographic factors, comorbidities, and concomitant medications, in BPH
patients in the United States. Safety outcomes, including AEs (common complaints), will also be
examined in this patient population.
Technical Approach: This is a prospective, multicenter, observational database to collect data on
the characteristics, management practices, and subject outcomes of men presenting to their
urologist or primary care practitioner with LUTS associated with BPH. It will be offered to a
geographically representative group of US physicians who will enroll BPH subjects that are
primarily managed conservatively (i.e. watchful waiting or medical intervention). In contrast to a
randomized, controlled trial, there are limited predefined interventions and the exclusion criteria
are limited. The physician makes his/her own clinical decisions; thus, data captured and reported
provide current practice patterns related to diagnosis, management, and results. The registry may
also assist physicians in subject follow-up and certain practice management tasks. The data
collected will serve to inform the medical community on optimal care. Recently, alpha testing of
the registry study was performed at approximately 20 to 30 sites to determine the feasibility of
completing the forms (i.e. the burden on subjects and physicians, and the sensitivity to the
wording of the sexual questions) during a single visit. Enrollment was competitive with a total of
approximately 200 to 300 subjects enrolled. The alpha-testing protocol has provided valuable
information that has been used in the design of this protocol for the full-scale registry. The full
scale registry is planned to include about 500 sites with approximately 7500 subjects with an
option to increase the number of sites, the number of subjects per site, and the registry duration.
The primary eligibility criterion is the diagnosis of LUTS associated with BPH at baseline
regardless of whether subjects opt for watchful waiting, treatment with 5-alpha-reductase
inhibitors or alpha-blockers, or combined medical therapy. Subjects who opt for invasive therapy
as an initial treatment or have had surgery in the past for BPH are not eligible for this study. This
registry may require minimal additional procedures or interventions as determined by the treating
physician. Subjects will be excluded if they decline participation; have concomitant lover urinary
tract disease or carcinoma, including history of carcinoma of the prostate or bladder; or have a
history of prostatic surgery, including minimally invasive procedures.
Progress: This protocol closed to enrollment, but remains ongoing to follow fifteen subjects
enrolled at MAMC.
523
Detail Summary Sheet
Date: 30 Sep 06 Number: 204086 Status: Ongoing
Title: Prospective, Open-Label, Non- Comparative, Multi-Center Study to Evaluate the Efficacy
and Safety of Ciprofloxacin Extended-Release (Cipro-XR) 1000 mg Tablets Given Once Daily for
7 to 14 Days in the Treatment of Patients 18 Years or Older with Complicated Urinary Tract
Infections Caused by Pseudomonas Aeruginosa and Other Common Uropathogens
Principal Investigator: MAJ Andrew C. Peterson, MC
Department: Surgery/Urology
Facility: MAMC
Associate Investigator(s): COL Robert C. Allen, MC; MAJ Keith J. O'Reilly, MC; MAJ Karen
C. Baker, MC; CPT Jack R. Walter, MC; CPT Brian J. DeCastro, MC; LTC Benjamin P. Harrison,
MC
Start - Completion:
Funding:
Periodic Review:
9/17/2004 - May 2005
Bayer via The Geneva Foundation
6/27/2006
Study Objective: To evaluate the safety and efficacy of Cipro XR® 1000 mg PO given once daily
for 7-14 days for the treatment of patients with complicated urinary tract infections caused by
Pseudomonas aeruginosa and other urinary pathogens. The primary efficacy parameter will be
bacteriologic outcome at the Test-of-Cure (Day +5 to +9 post-treatment) visit. Secondarily, clinical
response will be assessed at the Test-of-Cure (Day +5 to +9 post-treatment) visit. Clinical cure will
be correlated with bacterial eradication in the patient population valid for efficacy. The rate of
relapse between the Test-of-Cure visit and the late post-treatment (Day +28 to +42) visit will be
determined for patients with complicated UTI caused by P. aeruginosa. The safety of the drug
treatment will be monitored. To enroll a minimum of 8 patients with complicated UTI caused by P.
aeruginosa that is clinically and microbiologically valid.
Technical Approach: This is a prospective, open-label, multi-center, Phase IV clinical study to
evaluate the efficacy and safety of Cipro XR® 1000 mg PO once daily for 7-14 days for the
treatment of patients with complicated UTIs. Patients with clinical signs and symptoms of a
complicated UTI that meet all other entry criteria will be treated with Cipro XR® 100 mg PO once
daily for a planned treatment course of 7-14 days. Types of diagnoses most likely to be infected
with P. Aeruginosa at the time of a complicated UTI include: spinal cord injury/trauma, indwelling
urinary catheters (including transurethral and suprapubic), quadriplegia or paraplegia, multiple
sclerosis, other risk factors for complicated urinary tract infection and a previous history of a UTI
or asymptomatic bacteriuria with P. aeruginosa that was susceptible to flouroquinolones. Patient
screening will be performed within 48 hours prior to onset of therapy. During the 7 to 14 day
treatment period, there will be an office visit on Day 3-5 of therapy to assess clinical progress.
After completion of treatment, there will be a Test-of-Cure (Day +5 to +9 post-treatment) visit for
all patients, and for all patients with complicated UTI due to P. aeruginosa, a late follow-up (day
+28 to +42 post-treatment) visit to determine the rate of relapse. If, following a full course of
therapy, the investigator feels that continued antimicrobial drug therapy is warranted, the patient
must be classified as a treatment failure. Before required alternative antimicrobial drugs are
given, however, the patient must be fully evaluated and appropriate laboratory tests and cultures
performed so that the required information will be available in order to evaluate the study drug.
Progress: This protocol closed to enrollment with five patients enrolled. Three patients completed
the study, one patient screen-failed and one patient withdrew consent due to needing further
antibiotic treatment. The protocol remains ongoing pending a final site close out visit by the study
sponsor.
524
Detail Summary Sheet
Date: 30 Sep 06 Number: 203081 Status: Ongoing
Title: Study of the Safety and Effectiveness of the Mentor Two-Piece Inflatable Penile
Prosthesis, Protocol Number U108-802-4
Principal Investigator: MAJ Andrew C. Peterson, MC
Department: Surgery/Urology Facility: MAMC
Associate Investigator(s): MAJ Karen C. Baker, MC; ; MAJ Michael J. Sebesta, MC; CPT
Jennifer M. Pugliese, MC; MAJ Keith J. O'Reilly, MC; COL Robert C. Allen, MC
Start - Completion: Funding: Periodic Review:
7/10/2003 - Jun 2004 Mentor via The Geneva Foundation 5/23/2006
Study Objective: To demonstrate safety and effectiveness of Mentor's Two-Piece Inflatable Penile
Prosthesis in men who are undergoing surgical treatment of erectile dysfunction.
Technical Approach: This protocol is a multi-center trial. The baseline, pre-operative physical
and psychological assessment will serve as a control for each subject. Post-operative
measurements of penile erection and psychological assessment should provide a demonstration of
the efficacy associated with the penile implants. Patients will have the following baseline study
procedures within 30 days of surgery: medical history, physical exam, penile history and measure,
psychometric testing with patient satisfaction questionnaire (PSQ), investigators assessment of
erectile dysfunction. One or more of the following tests may be used to confirm the diagnosis of
erectile dysfunction: Doppler arterial flow, dynamic infusion cavernosometry, rigiscan, and snap-
gauge. The operative procedure will take place no more than 30 days after the baseline visit and
will record penile measurements and the device catalog number and lot number, anesthesia and
other procedure related information. There will be 3 post-operative follow-up evaluations
conducted 3-6 weeks after implantation, at 6 months, and 12 months. At each of these follow-ups
the following evaluations will be conducted: penile rigidity, adverse event evaluation, urinalysis
(12 month follow-up only), patient satisfaction questionnaire (6 and 12 month follow-up only),
penile rigidity will be adequate if it is sufficient for sexual intercourse, as determined by the
Investigator during postoperative exams and by asking the patient about his ability to perform
sexual intercourse. Safety assessment will include: incidence on a per subject basis of all
complications (e.g. device malfunctions or infection), time to occurrence of all complications. This
study will assess the psychological impact on the subject of implantation of the device. The
primary hypothesis will be tested by placing an exact two-sided 95% confidence interval on the re¬
operation rate. If the upper bound on this confidence interval is less than 0.193 than the null
hypothesis will be rejected in favor of non-inferiority to Alpha 1.
Progress: This study remains open to enrollment, with eleven subjects enrolled who have
completed the study.
525
Detail Summary Sheet
Date: 30 Sep 06 Number: 205088 Status: Ongoing
Title: The Value of Resistive Index: A Longitudinal Study of Confounding Variables and Their
Impact - A Pilot Study
Principal Investigator: CPT Jennifer M. Pugliese, MC
Department: Surgery/Urology Facility: MAMC
Associate Investigator(s): COL (Ret) Charles A. Andersen, MD; LTC Benjamin W. Starnes,
MC
Start - Completion: Funding: Periodic Review:
5/24/2005 - Dec 2008 DCI 5/10/2006
Study Objective: To determine the course and variability of resistive index as measured by
Doppler ultrasound in patients with new onset hypertension over time as their disease progresses
and new medications are added.
Technical Approach: In this prospective, observational study, a database containing
demographic and medical information will be constructed for patients with newly diagnosed
hypertension. Candidates for the study will be identified by their primary care providers and
referred to the vascular surgery clinic for consideration for the study. A baseline Doppler
ultrasound and resistive index calculation will be performed at that point prior to the initiation of
any medical therapy for their hypertension. A group of healthy volunteers will also receive a
Doppler ultrasound measured resistive index calculation as a control group. Doppler ultrasound
and resistive index calculations will then be undertaken at three month intervals in the study
patients as well as in the control group. We hope to better determine the utility and accuracy of
resistive index in diagnosing renal artery stenosis and determining which patients would benefit
from surgical intervention based on the information obtained from this study.
Progress: This protocol remains open to enrollment with no subjects enrolled. Recruitment
continues.
526
Detail Summary Sheets
Vascular Surgery, Department of Surgery
527
Detail Summary Sheet
Date: 30 Sep 06 Number: 206012 Status: Ongoing
Title: A Comparative Prospective, Randomized, Double-Masked, Parallel Group, Sham-
Controlled Trial of MIST Therapy for the Reduction of Pain in Chronic Lower Extremity Ulcers
Principal Investigator: COL (Ret) Charles A. Andersen, MD
Department: Surgery/Vascular Surgery Facility: MAMC
Associate Investigator(s): Mary Anne Landowski, MSN, RN; LTC Benjamin W. Starnes, MC;
Monica H. Schweinberger, DPM; Leslie B. Schoneman, PA-C; Gary P. Degen, DPM; Vickie R.
Driver, DPM; Thomas S. Roukis, DPM
Start - Completion: Funding: Periodic Review:
1/17/2006 - Apr 2006 Celleration, Inc. via Geneva Foundation 10/18/2006
Study Objective: Primary Objectives: Effectiveness (1) to assess the reduction in baseline
numeric pain rating scale scores comparing MIST Therapy in relation to sham control through
treatment week 4. Safety: (2) to compare the incidence of adverse events among patients receiving
MIST Therapy in relation to the sham control treatment group. Secondary Objectives: (1) to
compare the use of analgesic medication between the two treatment groups through treatment
week 4 and (2) to compare the quality of life scores using an SF-12v2 scale between the two
treatment groups through treatment week 4.
Technical Approach: The trial is designed as a comparative, prospective, randomized, double-
masked, parallel group, controlled, multi-center study of patients presenting with chronic non¬
healing lower extremity venous insufficiency, arterial or sickle cell ulcers. To be eligible for
randomization patients must complete a 14 day period of documented, stable, acceptable standard
of care under the care of the principal investigator and must demonstrate an average Visual
Analogue Scale (VAS) score of ?4 (Range 0 - 10), calculated from two VAS evaluations during the
last week of the 14 day lead-in phase. No VAS evaluation can be less than 3 and the two
evaluations cannot be different by more than three to be considered stable and eligible for
randomization. Patients will be allowed to take pain medications as needed during the lead-in
period and during the study protocol. Patients will also be allowed to use antibiotics during the 14
day lead-in period if deemed clinically necessary by the investigator. Patients will not be allowed
into the study while actively using antibiotics but can remain in the study if antibiotics are
clinically required later in the course of the trial. A patient who completes the 14 day documented
stable standard of care lead-in phase for the index ulcer(s), demonstrates a stable VAS average
pain score and who meets all other study inclusion/exclusion criteria will be randomized to receive
one of two treatment courses: a) standard of care with MIST Therapy or, b) standard of care with a
sham control. All patients will receive three treatments per week for 4 weeks. Patients must
receive 9 of the total 12 treatments and cannot miss more than two consecutive treatments to be
considered evaluable. Investigators will be allowed to use their own standard dressings as
appropriate for the moisture balance of the ulcer but these will only include standard hydrocolloid,
hydrogel, alginate or foam dressings. Changes from one type of dressing to another (e.g. alginate to
hydrocolloid) will be allowed as deemed necessary for moisture balance. No advanced or
impregnated dressings will be allowed during the study. No topical antibiotics or antibiotic
dressings (silver, iodine, etc) will be allowed. Following randomization, ulcer assessments, VAS
pain scales and adverse event assessment will be conducted at weekly intervals through week 4;
analgesic assessment will be performed three times per week on treatment days; Quality of Life
(QOL) scales will be conducted at baseline, week 2 and week 4; sharp debridement will be
performed only once per week if deemed necessary by the investigator.
Progress: This protocol remains open to subject entry. No subjects were treated during FY06. Two
subjects were screened; one screen failed. The other subject signed informed consent and began the
528
two-week pre-screening process, but was dropped as the subject did not meet all the eligibility
requirements (could not differentiate leg pain from stump pain). Other sites have had similar
difficulty enrolling.
529
Detail Summary Sheet
Date: 30 Sep 06 Number: 203079 Status: Completed
Title: A Double-Blind, Randomized, Parallel Group, Placebo- Controlled Study to Evaluate the
Safety and Efficacy of NM-702 in Subjects with Intermittent Claudication, Protocol Number
NCI-IC-0201
Principal Investigator: COL (Ret) Charles A. Andersen, MD
Department: Surgery/Vascular Surgery Facility: MAMC
Associate Investigator(s): Leslie B. Schoneman, PA-C; MAJ Philip S. Mullenix, MC; LTC
Benjamin W. Starnes, MC; MAJ Allen D. Rubin, MC; MAJ Tyler L. Seick, MC
Start - Completion: Funding: Periodic Review:
9/3/2003 - Jul 2005 Nissan Chemical Foundation via The Geneva 5/24/2005
Foundation
Study Objective: To determine if 4 mg and/or 8 mg NM-702 BID for 24 weeks significantly
improves peak walking time (PWT) when compared to placebo. To determine the safety and
tolerability of 4mg and 8 mg NM-702 for 24 weeks through analysis of adverse events, clinical
laboratory tests, electrocardiogram and physical examinations. To determine the dose-response
profile, specifically, to find out whether the 8 mg dose BID will demonstrate better efficacy
(improvement in PWT) than the 4 mg dose BID (e.g. the dose-response trend extends to 8 mg BID
level), providing a basis for optimal dose selection.
Technical Approach: This is a double-blind, parallel-group, dose-response study in which
subjects are randomized to receive either 4 mg or 8 mg of NM-702, or placebo, BID for 24
consecutive weeks. This study will look at males or females 50 years of age and older that have
been diagnosed with intermittent claudication. Approximately 25 patients will be enrolled into this
study here at MAMC. There will be a Screening Visit, three Baseline Visits at least 3 but no more
than 10 days apart, in order to obtain 3 baseline tests on separate days, Treatment Visit l(also
Baseline Visit 3) study drug for weeks 1-6 will be dispensed at this visit, Interim Visit 2 study
drug for weeks 7-12 will be dispensed at this visit, Interim Visit 3 study drug for weeks 13-18 will
be dispensed at this visit, Interim Visit 4 final study drug for weeks 19-24 will be dispensed at this
visit, a Primary Endpoint Assessment Visit 5 for primary safety and efficacy follow-up
assessments, Follow-up visit 6.
Progress: This protocol reached accrual goals and closed to enrollment in April 2005. A site close
out visit was conducted May 2006, with 49 MAMC patients consented/screened, 23 randomized
and 21 who completed the entire study period. Three subjects eventually withdrew consent.
Twenty internal serious adverse events and 17 external adverse events were reported, but none
whose relationship was related to study medication.
530
Detail Summary Sheet
Date: 30 Sep 06 Number: 206094 Status: Ongoing
Title: A Multi-Center, Double-Blind, Randomized, Parallel, Vehicle-and Standard Care-
Controlled, Dose-Ranging Study Assessing the Safety and Efficacy of MRE0094 Gel When
Applied Topically for 90 Days to Subjects with Diabetic, Neuropathic, Foot Ulcers
Principal Investigator: COL (Ret) Charles A. Andersen, MD
Department: Surgery /Vascular Surgery Facility: MAMC
Associate Investigator(s): Monica H. Schweinberger, DPM; LTC Benjamin W. Starnes, MC;
Mary Anne Landowski, MSN, RN; Thomas S. Roukis, DPM
Start - Completion: Funding: Periodic Review:
8/3/2006 - Dec 2006 King Pharmaceuticals Research and N/A
Development, INC via The Geneva Foundation
Study Objective: To assess the efficacy of 3 concentrations of MRE0094 gel compared to vehicle
gel and standard care on complete healing of chronic, diabetic, neuropathic, foot ulcers when
applied topically for up to 90 days.
Technical Approach: This is a multi-center, double-blind, randomized, parallel, vehicle-
controlled, and standard care-controlled dose-ranging study of topically applied MRE0094 in
diabetic subjects with chronic, neuropathic foot ulcers. Three concentrations of MRE0094 gel (5
g/g, 50 g/g, and 500 gig), a vehicle control gel, and a standard care arm using a hydrogel-based
product to provide a moist wound environment will be evaluated in a parallel design. About 300
subjects will be randomized in a 1:1:1:1:1 allocation into 5 parallel treatment arms (~60 subjects
per treatment arm) to obtain 290 evaluable subjects. Treatment arms will be MRE0094 gel 5 g/g,
50 g/g, and 500 g/g, vehicle gel, and hydrogel (as part of the standard care only arm).
Randomization will be stratified based on baseline wound size.
Each subject will complete a 14-day Screening/Standard Care Run-in (SSCR) Period, a Treatment
Period of up to 90 days, and a 28-day Posttreatment Period. Subjects who successfully complete all
SSCR Period assessments, and who meet all entry criteria will enter the Treatment Period and be
randomized to 1 of 3 concentrations of MRE0094 gel, vehicle gel, or hydrogel (as part of the
standard care only arm) using a central randomization procedure. MRE0094 gel, vehicle gel, or
hydrogel will be applied once daily to the target ulcer for up to 90 days. A11 wounds will be covered
with a saline-moistened gauze pad following each application of study drug. The dressing will be
held in place by wrapping it with rolled gauze, and taping gauze to gauze. A11 subjects will be
given comprehensive standard care for diabetic, neuropathic, foot ulcers during the entire study
that will include: (1) off-loading the target ulcer using an unaltered Bledsoe Diabetic Conformer
Boot plus crutches or wheel chair as needed; NOTE: subjects with Charcot's deformity may use
their Charcot Restraint Orthotic Walker in place of the Bledsoe boot, (2) maintaining a moist
wound environment; (3) reminding subjects of the importance of proper nutrition and adherence to
glycemic control measures instituted by their health care providers; (4) additional sharp
debridement if needed; and (5) infection control measures. Following the Treatment Period,
subjects will enter the Posttreatment Period. A11 subjects (with healed or non-healed ulcers) will
continue to be given standard care for their target ulcer as described above. Only subjects with
non-healed ulcers will apply hydrogel during the Posttreatment Period. Each subject will complete
up to 12 clinic visits over the course of the study during which procedures and assessments of
safety, efficacy, and protocol compliance will be performed.
Progress: Enrollment is pending a site initiation visit that is scheduled for Oct 31, 2006.
531
Detail Summary Sheet
Date: 30 Sep 06 Number: 205111 Status: Terminated
Title: A Phase 3, Randomized, Double-Blind, Multinational Trial of Intravenous Telavancin
Versus Vancomycin for Treatment of Complicated Gram Positive Skin and Skin Structure
Infections with a Focus on Patients with Infections Due to Methicillin-resistant Staphylococcus
aureus 0018
Principal Investigator: COL (Ret) Charles A. Andersen, MD
Department: Surgery/Vascular Surgery Facility: MAMC
Associate Investigator(s): LTC Benjamin W. Starnes, MC; Monica H. Schweinberger, DPM;
Gary P. Degen, DPM; Leslie B. Schoneman, PA-C; Mary Anne Landowski, MSN, RN; MAJ
Cecily K. Peterson, MC
Start - Completion: Funding: Periodic Review:
12/8/2005 - Jan 2006 Theravance via The Geneva Foundation 7/10/2006
Study Objective: To compare the efficacy and safety of telavancin to vancomycin in the
treatment of adults with complicated Gram positive skin and skin structure infections with an
emphasis in patients with infections due to MRSA.
Technical Approach: This Phase 3 study is a randomized, double blinded, active-controlled,
parallel-group, multi-center, multinational trial. Since the study is designed to enroll primarily
patients with infection due to MRSA, vancomycin is the comparator agent. Approximately 750
patients worldwide will be randomized to either telavancin lOmg/kg IV q 24 hours or vancomycin 1
g IV every 12 hours. In order to maintain the blind, dummy infusions will be used. The minimum
duration of study therapy will be 7 days and the maximum allowable duration of study therapy
will be 14 days for all patients. The duration of study therapy for each patient will be determined
by the investigator as clinically indicated and will continue until resolution of signs and symptoms
associated with the skin infection, or until improvement to such an extent that no further therapy
is deemed necessary, to a maximum of 14 days. Patients will be treated to intravenous therapy
throughout and may not be switched to oral therapy. However, when appropriate and necessary to
complete study therapy, patients who are initially hospitalized may be discharged and continue to
receive intravenous medication as an outpatient.
For patients with polymicrobial infections involving Gram negative and/or anaerobic bacteria in
addition to the Gram positive organism for which study medication is used, ONLY aztreonam and
/or metronidazole used in accordance with the manufacturer's package insert may be added to
study therapy. Investigators are encouraged to administer aztreonam and/or metronidazole in
patients with suspected or proven mixed infections.
Surgical management of the infection is permissible and considered standard of care; however,
significant surgical intervention, more than routine debridement, following initiation of the study
medication on more than 2 occasions during the study will constitute evidence of clinical failure.
The primary efficacy end point is the clinical response at the Test of Cure assessment. For the
purpose of analysis, assessment of "not cured" at End of Therapy will be carried forward to the
Test of Cure.
Progress: This protocol closed to enrollment before any subjects could be screened at MAMC. No
formal close out visit was required by the study sponsor since the site had never been activated.
The protocol terminated during FY06.
532
Detail Summary Sheet
Date: 30 Sep 06 Number: 200088
Status: Completed
Title: A Prospective, Randomized Study Comparing the Outcome of Carotid Endarterectomy
Using New Generation Dacron or Expanded Polytetrafluoroethylene (e-PTFE) Carotid Patching
Principal Investigator: COL (Ret) Charles A. Andersen, MD
Department: Surgery/Vascular Surgery
Facility: MAMC
Associate Investigator(s): LTC Benjamin W. Starnes, MC; COL David F.
LTC Stephen B. Olsen, MC
J. Tollefson, MC;
Start - Completion: Funding:
8/17/2000 - Jun 2002 Meadox Medicals via The Geneva Foundation
Periodic Review:
4/26/2005
Study Objective: The primary objective of this study is to compare the performance of the newest
generation Dacron and e-PTFE patches with respect to: (1) postoperative stroke/thrombosis, (2)
recurrent carotid stenosis and (3) intraoperative handling/blood loss.
Technical Approach: After informed consent, patients will be randomized to patch angioplasty
with either a Hemashield Finesse patch or a Gore-Tex Acuseal patch. Surgeons will rank the
handling of the patch on an analog scale. Time to cessation of bleeding will be monitored. Patients
will have an intraoperative duplex, and follow-up duplex examinations at 3, 6, 9, 12, 18 and 24
months after the operation. Rates for carotid re-stenosis will be determined. Perioperative and late
neurologic morbidity will be identified and determined.
Progress: This protocol was reported as completed in March 2006. Data collection and interim
analysis has been conducted on 71 patients that enrolled and completed the study visits. A final
report on the results of data analysis remains pending.
533
Detail Summary Sheet
Date: 30 Sep 06 Number: 202086 Status: Ongoing
Title: A Randomized, Controlled Multicenter Trial of Vacuum Assisted Closure Therapy™ in the
Treatment and Blinded Evaluation of Diabetic Foot Ulcers (Protocol VAC2001-08)
Principal Investigator: COL (Ret) Charles A. Andersen, MD
Department: Surgery/Vascular Surgery Facility: MAMC
Associate Investigator(s): Monica H. Schweinberger, DPM; Vickie R. Driver, DPM; Gary P.
Degen, DPM
Start - Completion: Funding: Periodic Review:
9/24/2002 - Aug 2005 KCI USA via The Geneva Foundation 5/23/2006
Study Objective: The primary objectives are to determine the incidence of complete ulcer closure,
accelerated ulcer closure or facilitation of surgical closure, and change in ulcer area. The secondary
objectives are to determine the reduction in complications, including amputations, quality of life,
and average total cost of care.
Technical Approach: This study will be looking at approximately 18 male or female patients, 18
years of age or older that have diabetic foot ulcers > 2cm2 in area after debridement. Visit #1-
Eligible patients will be given a physical exam, a relevant medical and surgical history will be
taken, concomitant medications will be listed, and blood drawn for laboratory tests and the patient
will be given a Quality of Life Questionnaire to complete. Visit #2, the patient will be randomized
and given their first treatment. At subsequent visits the study group patients will have medical
and medication histories updated, digital photographs will be taken of the wound, measurements
taken, dressing applied and instructions on continued care given. The control group will receive
standard of care treatment. All patients will receive off-loading therapy preventatively and
therapeutically as indicated. Off-loading therapy is used to keep pressure away from the wound
area by means of the use of a special shoe, boot, cane, or, in some cases, a wheelchair. No patient
will remain in the study for longer than 12 months (total duration). The wound will be examined
for recurrence or determination of ulcer status.
Progress: This protocol closed to subject entry in March 2006, with fourteen subjects enrolled, one
during FY06. Two subjects withdrew consent, one subject screen failed, two were dropped per the
advice of the principal investigator, one was lost to follow-up and nine completed the trial. The role
of PI was changed from Vickie Driver, DPM, to Charles Andersen, M.D., in December 2005. The
protocol remains ongoing pending study close-out by the sponsor.
534
Detail Summary Sheet
Date: 30 Sep 06 Number: 202115 Status: Completed
Title: A Randomized, Controlled Multicenter Trial of Vacuum Assisted Closure Therapy™ in the
Treatment and Blinded Evaluation of Amputation Wounds of the Diabetic Foot, Protocol No.
VAC2001-07
Principal Investigator: COL (Ret) Charles A. Andersen, MD
Department: Surgery/Vascular Surgery
Facility: MAMC
Associate Investigator(s): Vickie R. Driver, DPM; Gary P. Degen, DPM
Start - Completion: Funding:
12/23/2002 - Sep 2005 KCI USA via The Geneva Foundation
Periodic Review:
8/24/2005
Study Objective: The primary objectives are to determine the incidence of complete wound
closure, accelerated wound closure or facilitation of surgical closure, and change in wound area
over time. The secondary objectives are to determine the incidence of foot salvage, as defined by
retention of transmetatarsal amputation with no further revisions at end of study, incidence of
complications, quality of life, and average total cost of care.
Technical Approach: This study will be looking at approximately 8-10 male and female patients
18 years of age or older that have amputation wounds of the diabetic foot. Visit #1-Eligible
patients will be given a physical exam, a relevant medical and surgical history will be taken,
concomitant medications will be listed, and blood drawn for laboratory tests and the patient will be
given a Quality of Life Questionnaire to complete. Visit #2, the patient will be randomized and
given their first treatment. At subsequent visits the study group patients will have medical and
medication histories updated, digital photographs will be taken of the wound, measurements
taken, dressing applied and instructions on continued care given. The control group will receive
standard of care treatment. All patients will receive off-loading therapy preventatively and
therapeutically as indicated. Off-loading therapy is used to keep pressure away from the wound
area by means of the use of a special shoe, boot, cane, or, in some cases, a wheelchair. No patient
will remain in the study for longer than 12 months (total duration). The wound will be examined
for recurrence or determination of ulcer status.
Progress: A change of principal investigator was approved in January 2006, from Dr. Driver to
Dr. Andersen. This protocol was reported as completed at MAMC in February 2006, with nine
subjects enrolled. Six subjects completed the study and one was withdrawn. Two subjects died
before study completion; one subject on the control arm died of a seizure and the other died of an
MI, but was not on VAC therapy at the time of his death, having been removed from the study two
months earlier due to extensive comorbidity.
535
Detail Summary Sheet
Date: 30 Sep 06 Number: 203055 Status: Ongoing
Title: A Randomized, Controlled, Multicenter Trial of Vacuum Assisted Closure Therapy™ in
the Treatment and Blinded Evaluation of Pressure Ulcers, Protocol Number VAC2001-01
Principal Investigator: COL (Ret) Charles A. Andersen, MD
Department: Surgery/Vascular Surgery Facility: MAMC
Associate Investigator(s): ETC Benjamin W. Starnes, MC; Mary Anne Landowski, MSN, RN
Start - Completion: Funding: Periodic Review:
5/16/2003 - May 2004 KCI USA via The Geneva Foundation 1/24/2006
Study Objective: The primary objective of this study is to determine if topical negative pressure
therapy delivered by the Vacuum Assisted Closure device is clinically efficacious and cost effective
in the treatment of pressure ulcers.
Technical Approach: The study will look at 10 males or females, 18 years or older, who have the
presence of Stage III or Stage IV pressure ulcers located on the trunk or trochanter region. At Visit
1, the patient will have a relevant medical and surgical history taken; physical exam with height
and weight; concomitant medications recorded; blood drawn for lab tests. Visit 2 takes place 7days
after visit 1 -debridement and assignment to study or control groups will be done with a 1:1 ratio.
Study group will have the V.A.C. therapy; Control group will receive standard of care treatment.
Pain assessments are completed; data collected; digital photography; bi-layer tracing of the wound
will be measured; Granulation tissue formation will be categorically estimated in % and recorded;
wound assessment; Quantitative/Semi-Quantitative Bacterial Cultures performed; Patient will
complete the wound pain assessment. The VAS pain assessment will be done 1/2 hour prior and
post the wound dressing changes. Visits 3 through 7 (+/- 2 days) and 8 (+/- 7 days) - All patients
are placed on appropriate Group II or Group III bed surface; wound examinations and assessments
will be done: The same ulcer documentation will be done as in Visit 2 above, plus the Interim
dressing changes will be documented, i.e. average number of interim dressing changes calculated
per day and per week; a list of materials used are recorded; the occupation of the person
performing the dressing changes will be recorded. Visit 9 will be the first long term follow-up
assessment of recurrence. Visit 10 will be the second long term follow-up/End of Study visit. No
patient will remain on the study longer than 12 months (total study duration). The ulcer will be
examined for recurrence or determination of ulcer status and a VAS pain assessment will be
completed 1/2 hour before and 1/2 hour after the wound dressing changes.
Progress: This protocol remains open to enrollment, with 2 subjects enrolled who completed their
portion of the study procedures. One subject dropped out due to lack of efficacy. Investigators
anticipate the study sponsor closing this protocol by the first quarter of 2007.
536
Detail Summary Sheet
Date: 30 Sep 06 Number: 205010 Status: Ongoing
Title: Linezolid In The Treatment Of Subjects With Complicated Skin And Soft Tissue
Infections Proven To Be Due To Methicillin-Resistant Staphylococcus Aureus
Principal Investigator: COL (Ret) Charles A. Andersen, MD
Department: Surgery/Vascular Surgery Facility: MAMC
Associate Investigator(s): Gary P. Degen, DPM; LTC Benjamin W. Starnes, MC; Monica H.
Schweinberger, DPM; Vickie R. Driver, DPM
Start - Completion: Funding: Periodic Review:
3/3/2005 - Sep 2005 Pfizer via The Geneva Foundation 10/24/2006
Study Objective: Primary Objective: To compare the clinical efficacy of linezolid to vancomycin in
the treatment of complicated skin and soft tissue infections (cSSTI) due to MRSA in adult subjects
at the End of Study (EOS) visit. Secondary Objectives: (1) To compare the clinical efficacy, and
safety and tolerability of linezolid to vancomycin in the treatment of cSSTI due to MRSA in adult
subjects at the End of Treatment (EOT) visit. (2) To compare the bacteriological efficacy, and
safety and tolerability of linezolid to vancomycin in the treatment of cSSTI due to MRSA in adult
subjects at the EOT and the EOS visits. (3) To compare the medical resource utilization of linezolid
and vancomycin for this subject population.
Technical Approach: This is a Phase IV, multicenter, randomized, open-label, trial with two
treatment groups, linezolid IV or oral tablets and vancomycin IV infusion, to be administered for a
planned duration of 7-14 days of treatment. Subjects with documented MRSA bacteremia may be
treated up to 21 days at the discretion of the investigator. Subjects will be randomly assigned to
receive either linezolid intravenous (IV) infusion or oral tablets 600 mg every 12 hours or
vancomycin intravenous (IV) infusion 15mg/kg per dose every 12 hours in subjects with normal
renal function. Dosage and interval should be adjusted based on standard nomograms according to
renal function. Vancomycin levels should be performed at the investigator's discretion. Aztreonam
intravenous (IV) infusion 1-2 grams every 12 hours may also be administered as required for
suspected or proven Gram-negative pathogens until culture results are obtained. If the subject
does not have a Gram-negative pathogen, aztreonam will be discontinued, at the discretion of the
investigator. An alternative agent may be substituted for aztreonam if the local susceptibility
patterns preclude its use or for other reasons the subject may be unable to use it. The agent
selected must not have activity against MRSA. Metronidazole intravenous (IV) infusion or oral
tablets 500 mg every 8 hours may also be administered as required for suspected or proven
anaerobic pathogens until culture results are obtained. If the subject does not have an anaerobic
pathogen, metronidazole will be discontinued at the discretion of the investigator. Approximately
600 subjects per arm will need to be enrolled for a total sample size of 1200 subjects. There is no
planned formal interim analysis.
Progress: This protocol remains open to enrollment with eight subjects enrolled, three during
FY06. One subject is deceased (unrelated to study medication) and one subject discontinued. Three
subjects had MRSA.
537
Detail Summary Sheet
Date: 30 Sep 06 Number: 206071 Status: Ongoing
Title: Phase 3, Multicenter, Multi-National, Randomized, Double-Blind, Placebo Controlled
Study to Evaluate the Efficacy and Safety of Alfimeprase in Subjects with Acute Peripheral
Artery Occlusion (NAPA- 3)
Principal Investigator: COL (Ret) Charles A. Andersen, MD
Department: Surgery/Vascular Surgery Facility: MAMC
Associate Investigator(s): LTC Benjamin W. Starnes, MC; MAJ Kelly S. Blair, MC; Leslie B.
Schoneman, PA-C; LTC John D. Statler, MC; MAJ Joseph A. Ronsivalle, MC
Start - Completion: Funding: Periodic Review:
6/7/2006 - May 2007 Nuvelo Inc. via The Geneva Foundation N/A
Study Objective: To evaluate the efficacy of alfimeprase compared with placebo as measured by
30 day open vascular surgery free rate. To evaluate: rate of arterial flow restoration at 4 hours
after initiation of study drug, rate of improvement in index limb ankle-brachial index (ABI) by 0.15
at 30 days, change in Walking Impairment Questionnaire functional status scores from baseline at
30 days and safety.
Technical Approach: This is a Phase 3, multicenter, multi-national, randomized, double-blind,
placebo-controlled trial with the goal of randomizing 300 subjects. Eligible subjects will be
randomized in a 1:1 ratio to receive either intra-thrombus alfimeprase 0.3 mg/kg total dose or
intra-thrombus placebo. Study drug will be administered as split doses with 2/3 of the total dose
given as the first infusion followed in 2 hours by the remaining 1/3 of the total dose as a second
infusion. Both infusions will be given as 1 mL/min pulsed boluses. Subjects will receive both
infusions unless otherwise indicated. Study drug will be infused and subjects will be clinically
monitored and assessed by follow-up arteriogram 4 hours after initiation of the first dose of study
drug. Subjects with restoration of arterial blood flow on the 4-hour follow-up arteriogram will
receive no further intervention, endovascular therapy for underlying atherosclerotic lesions or
open vascular surgery. The decision to proceed to a particular intervention should be based on
functional, symptomatic, and/or physical examination criteria along with locally interpreted
arteriographic findings. Subjects without restoration of arterial blood flow seen on the 4-hour
follow-up arteriogram will only be eligible for open vascular surgery (e.g., thromboembolectomy).
Investigators will be instructed to follow the Acute PAO Management Algorithm (Section 3.4.2)
that was modified from the recommendations for the Ideal Management Algorithm for the
Treatment of Acute Limb Ischemia Due to Acute PAO. Thirty (30) day open vascular surgery free
rate will be the primary endpoint. Restoration of arterial flow rate, increase in ABI by 0.15 rate,
change in Walking Impairment Questionnaire (WIQ) functional status scores, and safety will be
the secondary endpoints. Restoration of arterial flow will be assessed by the investigator and by a
blinded, central Arteriogram Review Committee. Length of hospital stay and length of intensive
care unit (ICU) stay up to 30 days as well as WIQ scores and increase in ABI by 0.15 rate at 90
and 180 days after study drug infusion will be exploratory efficacy endpoints. Safety will be
assessed by monitoring of AEs, SAEs, major bleeding events, ICH, and peripheral arterial embolic
events up to 30 days as well as all cause mortality, AEs, surgical and endovascular procedures and
amputation at 30, 90, and 180 days.
Progress: This protocol is open to patient entry, with no enrollments during FY06. The study
sponsor indicates that enrollment in this study is slow. Study staff continues to monitor for eligible
subjects.
538
Detail Summary Sheet
Date: 30 Sep 06 Number: 205091
Status: Ongoing
Title: The Prevalence and Progression of Carotid Artery Stenosis
Radiation for Head and Neck Cancer
in Patients Undergoing
Principal Investigator: COL (Ret) Charles A. Andersen, MD
Department: Surgery/Vascular Surgery
Facility: MAMC
Associate Investigator(s): CPT Garth S. Herbert, MC; LTC Benjamin W. Starnes, MC; LTC
Douglas M. Sorensen, MC; LTC John B. Halligan, MC; CPT Michael J. Wilhelm, MC; Billinda
Tatum, RN, CCRC
Start - Completion: Funding:
6/16/2005 - Feb 2015 DCI
Periodic Review:
5/26/2006
Study Objective: (1) To establish the prevalence of carotid artery stenosis and its risk factors in
patients with head and neck cancer. (2) To establish the course of progression of carotid artery
stenosis in patients undergoing radiation for head and neck cancer. (3) To determine the
correlation (if any) of C-reactive protein levels with carotid artery disease in patients undergoing
radiation for head and neck cancer.
Technical Approach: This is a prospective cohort study. The screening tests are already being
offered by the Vascular Surgery Service at MAMC. Eligible patients would be consented and their
name, age, social security number, and other demographic data recorded in the ICDB and flagged
as a study participant. A short screening questionnaire (recorded in the initial ICDB note)
designed to identify other risk factors for or symptoms of carotid artery stenosis will be completed
at this time.
Patients referred to the Vascular Surgery Clinic at MAMC would have a screening carotid duplex
performed within one month of the initiation of XRT in order to establish the baseline level of
disease present in these patients. Each patient will also be asked to complete a questionnaire to
determine risk factors for and previous symptoms of vascular disease. The resultant data from
each duplex will be recorded in the patient's chart maintained at the vascular surgery clinic, and
the questionnaire will be kept in the chart as well. After performance of the carotid ultrasound, the
patient will be sent to the lab for blood draw to determine a baseline C-reactive protein level. After
radiation therapy, the dose of radiation administered to each carotid artery will be recorded. If a
hemodynamically significant stenosis is identified, the patient would be evaluated for a carotid
endarterectomy by ACAS and NASCET criteria, as is the standard of care in the Vascular Surgery
Clinic at MAMC.
After the initial screening, the patients will undergo follow-up carotid duplexes every six months
in order to define the progression of carotid artery disease following radiation therapy. As with the
initial duplex, any patient with a hemodynamically significant abnormality on follow up studies
would be evaluated for a carotid endarterectomy by ACAS and NASCET criteria. After the
screening, positive results requiring further diagnostic evaluation would be compiled and follow-up
would be arranged for definitive testing and subsequent risk factor modification and/or
intervention. These subjects will be identified as members of the "high risk" subgroup in terms of
future stroke potential to their primary care provider. Patients who agree to additional blood
draws will also have a C-reactive protein level determined on the same day the follow-up carotid
duplex is performed.
Progress: This protocol remains open to enrollment with three subjects enrolled who had a
carotid duplex performed prior to beginning radiation therapy. Given the small number of patients
enrolled thus far, as well as the fact that part of this study is longitudinal in that it will examine
539
changes in the degree of carotid artery stenosis following radiation, there are no findings or
conclusions thus far. All enrolled patients will continue to have screening carotid duplexes and
CRP levels drawn approximately every six months.
540
Detail Summary Sheet
Date: 30 Sep 06 Number: 203017 Status: Completed
Title: The Prevalence of Three Major Stroke Risk Factors in an Enrolled Medicare Population
Principal Investigator: COL (Ret) Charles A. Andersen, MD
Department: Surgery/Vascular Surgery Facility: MAMC
Associate Investigator(s): MAJ Philip S. Mullenix, MC; LTC Benjamin W. Starnes, MC; MAJ
Rosemary P. Peterson, MC; CPT Garth S. Herbert, MC; CPT Zachary M. Arthurs, MC; CPT
Katharine E. Wolcott, MC; CPT Daniel G. Cuadrado, MC; MAJ Allen D. Rubin, MC; Leslie B.
Schoneman, PA-C; MAJ Kelly S. Blair, MC
Start - Completion: Funding: Periodic Review:
6/18/0282 - Oct 2004 DCI 10/19/2005
Study Objective: (1) To establish prevalence of carotid stenosis in an enrolled Medicare
population. (2) To establish prevalence of atrial fibrillation in an enrolled medicate population. (3)
To establish prevalence of uncontrolled hypertension in an enrolled Medicare population.
Technical Approach: As part of a larger hospital-based total cardiovascular healthcare
initiative, this study is designed to establish the respective prevalence of significant carotid artery
stenosis, atrial fibrillation and hypertension in an enrolled Medicare population of 5000 men and
women over the age of 65. This project is designed as the first component of a three-phase stroke
screening and risk factor modification study to be performed over several years at MAMC. The
first phase will define the prevalence of these three conditions in the target population and
establish the participants in this study as tracked entities (each individually flagged as part of a
larger cohort) in the hospital's automated integrated clinical database system (ICDB). It is
estimated that this screening process will take approximately 36 months.
During the second phase, lasting 36 months per patient from time of initial screening, patients
identified to have carotid stenosis, atrial fibrillation or sub-optimally controlled hypertension will
have these conditions modified medically and/or surgically in accordance with the current practice
guidelines and standards of care in place at MAMC. During this period, the progress of this "high-
risk" subgroup will be tracked in the ICDB.
In the final phase, the longitudinal data acquired will be utilized to facilitate critical outcome
analysis of the risk-factor modification efforts performed in this high risk subgroup during phase
two.
Progress: This study has been conducted during the annual Retiree's Health Fair since November
2002, but there was no activity during FY06. Investigators are no longer gathering the type of
information generated from this study in this format. The protocol is considered completed. In
total, there have been 988 participants.
541
Detail Summary Sheet
Date: 30 Sep 06 Number: 206127 Status: Ongoing
Title: A phase 2B long-term, randomized, open-label, safety and tolerability trial comparing
[S,S]-Reboxetine (PNU-165442G) with routine care in patients with chronic painful diabetic
peripheral neuropathy (DPN) Study Number A6061031
Principal Investigator: Thomas S. Roukis, DPM
Department: Surgery/Vascular Surgery Facility: MAMC
Associate Investigator(s): COL (Ret) Charles A. Andersen, MD; Monica H. Schweinburger,
DPM
Start - Completion: Funding: Periodic Review:
11/17/2006 - Aug 2009 Pfizer via The Geneva Foundation N/A
Study Objective: Primary objective is to assess the long-term safety and tolerability of [S,S]-RBX
in patients with DPN.
Secondary objectives are to assess the effect of long-term treatment with [S,S]-RBX on neuropathic
pain and health-related quality of life in patients with DPN and to assess the effect of long-term
treatment with [S,S]-RBX on the use of pain-related medications for the management of DPN.
Technical Approach: This is a phase 2B long-term, randomized, open-label, safety and
tolerability trial comparing [S,S]-RBX with routine care in patients with DPN. Following the
screening visit (VI) is a one-week baseline period. At the end of this baseline period (V2), patients
meeting the randomization criteria are randomized to either [S,S]-RBX or routine care in a 1:1
ratio. Approximately 800 patients will be randomized at V2. The maximum trial duration is 2
years, during which there will be 14 clinic visits. Thereafter, a final clinic visit (V15) for follow up,
will be undertaken, one week after V14. Patients randomized to [S,S]-RBX will be treated with
lmg Q.D. for the first week after V2. At the end of this week they will return for another visit (V3),
where the dose may be left at lmg or, if required for symptomatic reasons, may be increased to
2mg. Thereafter, if required for symptomatic reasons, stepwise dose increase in lmg increments,
up to a maximum total daily dose of 8 mg, will be possible. For reasons of tolerability, the dose
may also be reduced in lmg decrements to a minimum total daily dose of lmg. Dose adjustment
may occur either at a scheduled clinic visit, or at an unscheduled visit. Following dose adjustment,
the patient will be contacted by telephone, within one week, to assess tolerability of the new dose
level.
Patients randomized to routine care will receive treatment optimized for them on an individual
basis. The investigator will be free to provide whatever pharmacological (other than
reboxetine/Edronax or opioidsf) or other treatment considered optimal for management of the
patient's pain, taking into consideration any side effects associated with this individualized
therapy. A centralized interactive voice response system will be employed to manage
randomization and the allocation of trial drug treatment. Subject to IRB/EC approval/favorable
opinion, this trial will include an additional research component involving collection of biological
samples for de-identified genetic analysis. The Clinical Pharmacogenomics Supplement to this
protocol provides a description of this additional research. Subjects may participate in this trial
even if they choose not to participate in the pharmacogenomics component.
Progress: This greater than minimal risk protocol received initial approval with stipulations
during the convened IRB meeting on 26 September 2006.
542
Detail Summary Sheet
Date: 30 Sep 06 Number: 206111 Status: Ongoing
Title: Pivotal Study to Evaluate the Efficacy and Safety of Dermal - Living Skin Replacement
(Dermal - LSR) in the Treatment of Chronic Diabetic Foot Ulcers
Principal Investigator: Thomas S. Roukis, DPM
Department: Surgery/Vascular Surgery Facility: MAMC
Associate Investigator(s): COL (Ret) Charles A. Andersen, MD; Monica H. Schweinberger,
DPM; Mary Anne Landowski, MSN, RN
Start - Completion: Funding: Periodic Review:
10/18/2006 - Feb 2007 ApoPharma Inc. via The Geneva Foundation N/A
Study Objective: The primary effectiveness objective is to determine the efficacy of Dermal -LSR
plus Standard of Care (SOC) for the treatment of chronic diabetic foot ulcers (DFUs) in comparison
to treatment with SOC alone. The primary safety objective is to determine the safety of Dermal -
LSR plus SOC for the treatment of chronic DFUs in comparison to treatment with SOC alone.
Technical Approach: This study will be a pivotal, prospective, randomized, controlled, open-
label, multi-center study that will evaluate the effectiveness and safety of topically applied Dermal
- LSR in chronic diabetic foot ulcers. The study has an open-label design, with the Investigator
and the subject being aware of the treatment group to which a subject is assigned. Subjects will be
randomized equally to two groups and receive either four topical applications (one per week for up
to 4 weeks) of Dermal - LSR in addition to standard of care or will receive standard of care only.
There will be a 2-week screening period. Following the consent process and randomization,
subjects will be treated according to assignment. Subjects assigned to Dermal - LSR + standard of
care will receive one application weekly for up to 4 weeks (or until the ulcer heals, whichever is
sooner). All subjects will receive standard of care for the entire study. If the ulcer heals by week 12
or sooner, subjects will be assessed at 1, 4 and 8 weeks post closure. If ulcer does not heal by week
12, subjects will be assessed weekly and will receive standard of care until week 20. If the ulcer
heals between weeks 13 and 19, subjects will be assessed one week post closure and at week 20 for
the final study visit. Note that if the ulcer heals at week 19, the one week post closure visit and the
final study visit will occur together at week 20. Telephone contact will be made 3 days (±1 day)
following each treatment visit (for weeks lto 4) to assess the well-being of the subjects. Telephone
contact will also be made in weeks 5 and 6. The Biostatistics Group from ApoPharma Inc. will
generate the randomization scheme.
Progress: This greater than minimal risk protocol received initial approval with stipulations
during the convened IRB meeting on 25 July 2006. CIRO approval was obtained 18 October 2006.
543
Detail Summary Sheet
Date: 30 Sep 06 Number: 206070 Status: Ongoing
Title: A Two-Part, Multicenter, Randomized, Double-Blind, Placebo-Controlled, Study to
Evaluate the Effect of Simvastatin, Losartan, and Pioglitazone on Cardiovascular Disease
Biomarkers in Lower Extremity Atherosclerotic Plaque Excised from Patients with Peripheral
Arterial Disease
Principal Investigator: LTC Benjamin W. Starnes, MC
Department: Surgery/Vascular Surgery Facility: MAMC
Associate Investigator(s): COL (Ret) Charles A. Andersen, MD; MAJ Kelly S. Blair, MC;
Leslie B. Schoneman, PA-C; MAJ Joseph A. Ronsivalle, MC; LTC John D. Statler, MC; CPT
Randy J. Kjorstad, MC; CPT Zachary M. Arthurs, MC
Start - Completion: Funding: Periodic Review:
6/5/2006 - Jul 2006 FoxHollow Technologies, Inc. via The Geneva N/A
Foundation
Study Objective: To assess the effect of 6 weeks of treatment with simvastatin, losartan or
pioglitazone on the RNA expression profile of atherosclerotic plaque excised from peripheral
arteries in the lower extremity of patients with PAD. To assess the effect of 6 weeks of treatment
with simvastatin, losartan or pioglitazone on protein and lipid biomarkers in atherosclerotic
plaque excised from peripheral arteries in the lower extremity of patients with PAD. To correlate
plaque protein and lipid biomarker changes following 6 weeks of treatment with simvastatin,
losartan or pioglitazone with changes in circulating plasma and/or serum biomarkers and with
blood gene expression profiling.
Technical Approach: This is multicenter, randomized, double-blind, placebo-controlled, 6-week
study, consisting of 3 separate sub-studies in which patients undergoing bilateral lower extremity
peripheral artery atherectomy will receive one of three drugs known to have beneficial effect on
the risk of cardiovascular disease. Patients will be selected for the particular substudy based on a
series of entry criteria and then randomized to the particular agent or placebo for 6 weeks.
Following successful completion of a 1 to 2 week placebo run-in period, patients with bilateral
symptomatic PAD requiring bilateral revascularization will undergo a unilateral atherectomy
using the SilverHawk™ device. The choice of left or right extremity will be determined by random
assignment. If treatment of one extremity in advance of the other is indicated either by patient
status or physician interest, the investigator will contact the study sponsor to determine whether
the patient should be entered. All plaque excised from a given extremity will be collected as part of
the study. Based on medical history and concomitant medications, patients will be assigned to one
of three treatment groups (simvastatin, losartan, or pioglitazone), and will be randomly allocated
to the active drug or matching placebo for a period of 6 weeks. Patients will then undergo repeat
peripheral atherectomy on the contralateral leg. A telephone follow-up will be made at Week 8.
Blood for gene expression profiling and plasma/serum for circulating biomarkers will be taken at
Week 0 and 6. Because of the differential handling of plaque for RNA expression profiling and
protein/ lipid measurements, it is not possible to perform both assessments on the same plaque
sample. Therefore, the study will be divided into 2 essentially identical parts. In Part A plaque will
be evaluated by gene expression profiling. In Part B plaque will be evaluated for protein and lipid
biomarkers. An equal number of patients will be enrolled in each Part. After the defined number of
patients have been enrolled in Part A for 1 of the 3 study drugs (and its placebo), patients who
meet the inclusion and exclusion criteria for that study drug (and its placebo) will then start
enrollment in Part B. A total of 336 patients will be enrolled, with a goal of approximately 300
patients completing the study. Each of the treatment groups (simvastatin, losartan, and
pioglitazone) will enroll 112 patients, 56 on active drug and 56 on placebo, with the intention of
achieving 50 completed patients on active drug and 50 completed patients on placebo. Parts A and
544
B will each include 28 patients on active drug and 28 patients on placebo, with the intention of 25
completed patients on active and 25 on placebo.
Progress: This protocol is open to patient entry, with no patients enrolled during FY06. Active
pre-screening for this clinical trial continues.
545
Detail Summary Sheets
Weed Army Community Hospital
546
Detail Summary Sheet
Date: 30 Sep 06 Number: 205049 Status: Completed
Title: A Phase 2 Study to Evaluate the Reactivity and Tolerability of Intradermally
Administered Doses of Coccidioidin in Human Subjects in a Target Population
Principal Investigator: ETC Gary A. Wheeler, MC
Department: WACH Facility: MAMC
Associate Investigator(s): CPT Karen C. Daily, MC; CPT Arman Faravardeh, MC
Start - Completion: Funding: Periodic Review:
8/10/2005 - Jun 2005 Weed ACH 2/22/2006
Study Objective: The primary objective of this study of intradermally administered coccidioidin
is to determine the prevalence of reactivity to this skin-test antigen in a target population located
in a region highly endemic for coccidioidomycosis. The study will also collect safety and tolerability
information for the test agent coccidioidin following administration of doses to normal human
subjects, as well as the reactivity tot he thimerosal preservative n the trace-thimerosal vehicle
control.
Technical Approach: This is a prevalence and incidence study of coccidioidomycosis conducted in
a target population of personnel living in a highly endemic area at Ft. Irwin. 150 volunteers will be
tested in a single test period, with the entire study lasting approximately 12 weeks. A single
dilution of test agent coccidioidin will be administered along with a vehicle control with trace
thimerosal (matching the concentration of the preservative in the coccidioidin). Both test agents
will be administered intracutaneously in a double blind fashion, and induration reactions will be
measured at 48 hours after injection. Subjects will be evaluated during the test period for adverse
events and 5-7 days after the injection for their resolution. All demographic and baseline
characteristics of these subjects will be described utilizing summary statistics of mean, standard
deviation and median for continuous factors and frequencies for categorical data.
Progress: This protocol was completed during FY06, with 120 subjects enrolled; 107 evaluable
and 13 lost to follow-up. Subjects were healthy men and women active-duty Soldiers between 18
and 55 years of age who were presumed to be at high exposure risk for coccidioidomycosis because
of their training activities in an area endemic for this disease. Each subject received two
intradermal injections concurrently and was observed for two hours post-injection. Subjects
returned to study site for examination at 48 hours. Follow-up was scheduled at 5-7 days post¬
injection. Safety: No clinically significant adverse events were seen during the study. Nine of the
107 subjects (71%) who returned for reading of the skin test reaction reported at least one event
during the study period. Six reported symptoms judged to be "local, mild", most commonly
transient tenderness and pruritis consistent with a positive DTH response. One subject reported
lightheadedness that resolved without intervention; this subject did not have a positive DTH
response. One subject reporting pruritis was treated with topical steroids. The investigators
considered all "local, mild" AE's in the study to be probably related to test agent. Thirteen subjects
failed to return for the 48 h reading and those successfully contacted reported no adverse events.
Activity: In the study, six subjects were reactive to both the thimerosal-containing vehicle and
coccidioidin at 48 hours rendering the coccidioidin data uninterpretable. Nine of 101 (8.9%)
subjects reacted with a positive (>5mm) induration response at 48 hours to coccidioidin alone.
Excluding one subject (#11) who had lived in Tucson and Texas for 26 years but had only been
based at Fort Irwin for ten months prior to the study, the overall reactivity rate was 8.0% (8 of 100
subjects).
Conclusions: Coccidioidin was well tolerated under the conditions of the study. Based on the sum
547
of induration data from the 48 hour interval, evaluable subjects with a positive DTH response to
coccidioidin had a mean sum of induration of 27.22 + 7.07 mm, and a median of 24 mm. Excluding
subject #11 yielded a mean of 27.00 + 8.01 mm and a median of 23 mm.
548
M. Protocol Number Index
203016
472
204040
339
200018
335
203017
541
204042
464
200032
310
203024
323
204043
183
200036
139
203030
236
204044
174
200040
142
203034
404
204045
213
200048
336
203035
482
204049
434
200049
328
203036
441
204051
440
200065
444
203041
282
204052
152
200077
311
203042
516
204058
380
200084
161
203045
275
204062
219
200088
533
203046
341
204064
156
200120
147
203048
220
204066
141
200125
445
203052
294
204069
366
200139
312
203053
505
204070
474
201015
439
203055
536
204072
182
201020
413
203066
270
204073
163
201054
330
203067
269
204074
289
201104
243
203075
79
204078
521
201107
484
203076
76
204079
500
201108
326
203077
391
204080
193
201112
459
203078
273
204082
199
201113
483
203079
530
204084
241
201121
486
203081
525
204085
430
201136
149
203084
151
204086
524
201137
150
203090
376
204087
83
201300
113
203091
422
204088
271
202010
143
203092
74
204089
353
202012
144
203095
281
204091
492
202013
398
203097
222
204094
155
202043
186
203099
277
204096
175
202048
212
203105
337
204097
301
202065
502
203107
377
204098
452
202066
239
203114
402
204100
410
202073
418
203116
81
204101
409
202074
162
203119
303
204104
287
202075
244
203122
68
204106
383
202083
176
204001
399
204107
177
202086
534
204005
487
204108
278
202088
181
204006
173
204111
267
202089
179
204008
191
204112
251
202091
460
204009
462
204114
172
202107
194
204010
66
204116
509
202114
178
204013
379
204117
92
202115
535
204025
493
204120
498
202117
363
204028
340
204121
496
202122
520
204031
242
204122
488
202300
112
204032
523
204123
153
203001
276
204034
154
204124
180
203014
286
204035
184
205004
215
549
205005
272
205084
321
205140
254
205006
491
205086
512
205300
446
205007
120
205087
168
206002
248
205009
477
205088
526
206004
427
205010
537
205089
274
206006
433
205013
454
205090
107
206008
233
205014
325
205091
539
206009
455
205015
313
205092
480
206010
412
205016
167
205093
165
206011
354
205017
495
205094
118
206012
528
205019
358
205095
315
206013
196
205021
279
205096
387
206014
166
205024
369
205097
390
206015
385
205025
98
205098
389
206016
403
205026
317
205099
351
206018
372
205027
515
205102
283
206019
95
205031
71
205103
100
206020
471
205032
227
205104
207
206021
302
205033
506
205105
331
206022
437
205034
297
205107
223
206023
116
205035
160
205108
109
206024
507
205036
197
205110
304
206025
198
205037
240
205111
532
206026
411
205038
211
205112
394
206027
414
205039
203
205113
396
206028
86
205040
499
205114
397
206029
264
205042
284
205115
225
206030
473
205044
72
205116
513
206031
518
205046
201
205117
237
206032
374
205047
324
205118
224
206033
350
205049
547
205119
494
206034
319
205050
467
205120
468
206035
299
205051
368
205121
217
206036
443
205052
463
205122
318
206037
438
205053
447
205123
202
206038
424
205054
451
205124
91
206039
497
205063
417
205125
415
206040
400
205065
300
205126
416
206041
401
205067
316
205127
420
206042
253
205068
314
205128
230
206043
419
205069
327
205129
479
206044
466
205070
170
205130
94
206045
338
205071
185
205131
104
206047
405
205072
481
205132
103
206048
97
205073
511
205133
90
206049
291
205074
386
205134
367
206050
85
205075
381
205135
517
206051
308
205076
504
205136
503
206052
305
205079
456
205137
295
206053
364
205080
408
205138
292
206054
189
205083
435
205139
298
206055
195
550
206056
346
206095
306
84033
257
206057
476
206096
307
84074
258
206058
465
206097
309
86089
259
206059
87
206098
265
87028
261
206061
423
206099
268
87091
262
206062
357
206100
489
87104
260
206063
84
206101
388
89080
121
206064
205
206102
522
90027
122
206066
347
206103
119
90029
123
206067
99
206104
102
90056
124
206068
157
206105
93
91094
158
206069
209
206106
371
93032
126
206070
544
206107
247
93063
263
206071
538
206108
246
93097
128
206072
490
206109
75
93136
129
206073
190
206110
392
93166
130
206074
349
206111
543
94092
332
206075
221
206112
187
94163
134
206076
431
206113
115
94170
131
206077
361
206114
426
95003
132
206078
88
206115
406
95058
333
206079
421
206116
425
95093
133
206080
105
206117
519
96095
135
206081
449
206118
360
96097
334
206082
450
206119
204
96118
136
206083
228
206120
448
97070
145
206084
192
206121
65
97096
125
206085
442
206122
69
98090
329
206086
229
206123
375
98112
137
206087
208
206124
432
99014
138
206088
359
206125
470
99019
159
206091
77
206126
171
99040
146
206092
344
206127
542
99071
140
206093
235
81035
255
99077
266
206094
531
81105
256
551
N. Annual Report Distribution List
Defense Technical Information Center
8725 John J. Kingman Rd. #944
Fort Belvior, VA 22060-6217
Clinical Investigation Regulatory Office
ATTN: MCCS-GCI
CDR AMEDDC&S
1608 Stanley Road
Ft Sam Houston, TX 78234-6125
Commander
USA Medical Research and Materiel Command
ATTN: MCMR-RCQ-HR
504 Scott Street
Fort Detrick, MD 21702-5012
CDR Brooke Army Medical Center
ATTN: MCHE-CI
Ft Sam Houston, TX 78234-6200
CDR Dwight D. Eisenhower AMC
ATTN: MCHF-CI
Ft Gordon, GA 30905-5650
CDR Madigan Army Medical Center
ATTN: MCHJ-CI
Tacoma, WA 98431-1100
CDR Tripler Army Medical Center
ATTN: MCHK-CI
Honolulu, HI 96859
CDR Womack Army Medical Center
ATTN: MCXC-FM Box 63H
Ft Bragg, NC 28307-5000
CDR William Beaumont AMC
ATTN: MCHM-DCI
El Paso, TX 79920-5005
CDR Walter Reed Army Medical Center
ATTN: MCHL-CI
Washington, DC 20307-5000
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552
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